One of the things that confused me the most when I switched to the Mac platform was the fact that there's no built-in way to lock the computer manually with a hotkey when walking away from it. This is something that was drilled into me from working in an office full of pranksters where leaving your computer unlocked was virtually a guarantee that you would be hosting a party for all of your co-workers that coming weekend.
It turns out that this is an oversight in Mac OS X, and a 3rd party utility is required to be able to lock your computer with a hotkey. For a simple solution I would suggest installing a very basic preferences pane called LockTight.
LockTight does exactly what you're looking for: assign a specific hotkey that when pressed will lock your Mac, requiring a password to unlock it if you have it configured to require a password to wake from sleep or screen saver (which you should).
Update: Reader Chad reminds us that if you actually want your machine to go to sleep with a keystroke (as opposed to simply locking the screen) you can use the Option-Cmd-Eject key combo.