Most modern gaming mice these days have at least five buttons — left, right, center (scroll wheel), and two thumb buttons. Even ultralight, performance-focused mice that ditch frivolous features such as Bluetooth connectivity and RGB lighting, like Logitech's G Pro X Superlight 2 and Razer's Viper V3 Pro have at least five buttons (and if you count the DPI switch button on the bottom, they actually have six). It's safe to say the world has moved beyond thinking that a mere two or three mouse buttons is sufficient (I refuse to acknowledge any company that has ever thought that only one mouse button was enough).
But five (or six, technically) mouse buttons isn't enough, either, and most flagship, all-purpose gaming mice have more than the five (now) standard buttons. Razer's Basilisk V3 Pro 35K, for example, has 13 programmable controls, though not all of these are buttons (this number includes the tilt wheel, which allows you to remap the center, right, and left clicks, as well as the scroll up/down functions); so does Logitech's G 502X Plus.
You might be thinking, "Surely, 13 programmable controls — or 11 programmable clicks, if we're not counting the scroll directions — is more than enough," but it's not — in fact, it's not much more than five or six, functionally speaking.
Saying these mice have 13 programmable controls is a bit disingenuous — while all of the buttons can technically be remapped, it's safe to say that almost nobody is going to remap the standard left and right primary buttons or the scroll function. They probably aren't even going to remap the two thumb buttons, which are mapped to MB4 and MB5 by default. And any buttons on the underside of the mouse might be remappable, but they're not usable mouse buttons in the midst of gaming (or anything). Once you take these buttons off the table, you're left with just a couple of actual extra buttons — both of these mice have a third "trigger" button in the thumb area (often used to temporarily slow down DPS for when you're lining up a tricky shot).
But don't worry — there are mice with even more buttons. Specifically, mice like the Razer Naga V2 Pro, the Corsair Scimitar Elite SE Wireless, and the SteelSeries Aerox 9 Wireless, all of which have a 12-button side panel (or, well, the option of a 12-button side panel), for all your actual mouse button needs.
Mice with 12-button side panels are usually aimed at a particular niche of gaming: players of MMORPGs (e.g., The Elder Scrolls Online) and MOBAs (e.g., League of Legends). Both MMORPGs and MOBAs are about action and inventory management — you need a lot of hotkeys/mouse buttons to open up various menus and execute however many different types of attacks or skills the game allows for. Sure, you can use your keyboard — and, well, you'll have to, as there are far more hotkeys in any of these games than you can fit on a mouse — but many things are more convenient to do from your mouse (especially if it's a shortcut that can be set up as a macro), and it's just more efficient, in general, to have both hands in the game.
But you don't need to be playing an MMORPG or a MOBA for those extra mouse buttons to come in handy: not only do most games have at least some sort of inventory system that requires management — even if it's just swapping and/or reloading weapons — but there are plenty of other things you might need to do while gaming. There are also plenty of useful shortcuts that can be mapped to your mouse buttons for when you're not gaming at all — having 12 easily-accessible macro keys is fantastic for productivity, if you use them.
Plus, if you're using a multi-button mouse built by a mainstream gaming company, the supporting peripheral software will usually allow you to set up game- and app-based profiles that switch based on your current active window. This can be finicky, however — as most peripheral softwares is — so I prefer to map my mouse buttons to generic extra modifier keys (e.g., F13, F14, etc.) and assign specific actions in each game's in-game menu. This only works for actions that can be remapped within the game, of course — anything else, you'll need to map directly to the mouse.
Autorun
You do a lot of walking/running when you're exploring large open-world games — a lot. MMORPGs like World of Warcraft and The Elder Scrolls Online have an autorun feature — a hotkey that lets you toggle forward movement, so you can move without having to hold down the W key for hours. While it's usually bound to something obscure on the keyboard (or not bound at all) by default. I'm pretty sure binding ESO's autorun to one of my mouse buttons saved me from a repetitive stress injury.
Primary Action / Interaction
Once you start using autorun, it's very frustrating to run up to an interactive character or object, only to have to find the interaction key on your keyboard (usually E, R, or F — conveniently close to the WASD movement keys, which you are no longer using). The only solution, of course, is to map that action to another mouse button, so you can now run up to things and interact with them without ever touching the keyboard. While you're at it, you may as well also map a third button to the Esc key — so you can also easily leave those interactions without touching the keyboard.
Volume Control
Many of the best gaming keyboards come with volume knobs (and other dedicated media controls) — but I don't have time to find and fiddle with a knob when my husband is trying to talk to me over my dogs barking. I usually assign two of the less-convenient buttons in the 12-button cluster to volume control (volume up and volume down, though you could also assign one button to mute. I don't use it so often that it needs to be foolproof, but I've never regretted mapping volume controls to my mouse.
Print Screen / F12 / Screenshots
The default screenshot hotkeys — Print Screen for Windows, and F12 for third-party apps like Steam and ReShade — are not in a particularly convenient location. Some might argue that lightning-quick screenshot-taking isn't a critical aspect of gameplay, but I beg to differ. You don't want to have to fumble across your keyboard to find the Print Screen button when the perfect Kodak moment pops up; you just want to be able to quickly hit a mouse button and keep going. And if you're using fancy camera tools like Frans Bouma's photomode mods, mapping your screenshot key to a mouse button is a must.
Push-to-Talk
If you stream while playing games, or you play games while chatting with friends over voice chat — and especially if you do both at the same time — you're probably using either push-to-talk or a mute toggle to control who's hearing your audio, and when. Push-to-Talk and other microphone-related hotkeys are basically made to be mapped to your mouse, as talking is essentially a way to bypass typing. You can also map a hotkey for a game chat overlay to your mouse, but it's hard to avoid the keyboard in a text chat.
Modifier Keys
Okay, you can't avoid touching the keyboard forever. But you can make your keyboard significantly more efficient and one-handed by moving modifier keys — Ctrl, Fn, Shift... and the Windows key — to your mouse. Now, instead of having to use two hands to perform Fn shortcuts, you can hold down a mouse button with one hand and pump out those secondary keybinds like nobody's business.
App-specific Shortcuts
Multiple mouse buttons aren't just convenient and efficient in games — they can make powerful productivity tools, and you can usually set up app-specific profiles similar to the gaming-specific profiles using peripheral software. Anyone who uses a complex, shortcut-heavy app — basically any photo-, video-, or sound-editing software — knows how useful it would be if you could perform some of those shortcuts with the click of a mouse button. The exact shortcuts you should program on your mouse depends, of course, on what you're doing — whether you need a shortcut to quickly change brush size and opacity, or you just need shortcuts to quickly move between tools.
Managing Windows and Tabs
The most frustrating thing about having a large, high-resolution screen — or multiple large, high-resolution screens — is managing windows and tabs (it's hard enough to just find your mouse with multiple screens). Mapping your mouse buttons to standard tab and window management keyboard shortcuts, such as Ctrl + Tab (to move to the next tab) or Ctrl + Shift + Tab (to move to the previous tab), or Ctrl + W (to close the current tab) can save you a lot of time and hassle, so long as you take the time to learn the buttons. (But you probably still don't want to start with the close tab shortcut — just in case.) Also, any task that requires you to either use a keyboard shortcut or find your mouse and move it very precisely somewhere on screen is worth considering (e.g. "Show Desktop").
What not to map to mouse buttons
Take a look at any gaming peripheral software and you'll see that there are several different types of keys and actions that can be mapped — some you may not have realized were options, and some you may not have wanted as options (I'm pretty sure Asus gives you the specific option of mapping Armoury Crate somewhere, as though anyone is so desperate for Armoury Crate that they'll dedicate an entire button to it (not to mention the fact that, if Armoury Crate isn't running, you probably won't be able to open it on an Asus-made peripheral until Armoury Crate is running). Just like you probably don't need to manually switch your Razer Chroma RGB lighting effects so often that you want to dedicate an entire mouse button to it — not even if you have a dozen mouse buttons.
More generally speaking, however, while it might seem neat that you can set a mouse button to open a program or a website for you, this is probably not all that useful in a gaming or productivity context, since you normally don't need to open a program more than... once or twice in a single session. You also probably don't need to map more than one DPI or profile switch button, as it usually makes sense to just cycle through those. Individual keys that aren't associated with shortcuts aren't terribly useful, either — but text strings, if used often enough, can definitely be worth it. One of my mouse buttons is programmed to type "site:tomshardware.com " — space included, for quick, site-specific searches, but other text strings that come to mind are those that contain unusual characters or punctuation. I do have one of my mouse buttons programmed to insert an em-dash, for the rare occasion that I'm using a keyboard without a numberpad.
I know plenty of people will insist that five or six buttons is more than enough, and that they wouldn't even know what to do with 12 buttons — let alone 19. All those buttons can be pretty intimidating, and it does take some time and experimentation to get a 19-button mouse set up perfectly, for you. But if you do put in the effort and take full advantage of how customizable gaming mice — and most peripherals, actually — are today, you'll quickly find that 19 buttons isn't nearly enough.
