I have two monitors attached to a 8800GTS-512. When I play civilization-4 I can select either full screen mode, or windowed mode in the game options. In full screen mode, my cursor does not go past the boundaries of the main monitor, which is the best way to play. If I get an e-mail, it pops up on the second monitor. If I want to break out of the game, I push the windows pearl button, and the game minimizes, and I can do what I want.
Alternatively, in windowed mode, you can point to the window of choice, but some of the full screen map scrolling options can't be done. I would imagine that exactly how this is done will differ, depending on the game.