When running a Cocoa application, you can control-click on any word and select "Look up in Dictionary" from the pop-up menu. This will invoke the new Dictionary application, which will define the selected word. While this is handy, there's an even quicker method (undocumented, as far as I can tell).

Instead of selecting the word, hover the mouse over the word and press Command-Control-D. This will pop-up a a mini-dictionary at the mouse location, containing the word's definition, as seen at right.

Also, if you keep Command-Control pressed, the popup definition window will follow the mouse, showing a definition of any word the mouse visits.

[robg adds: If you prefer the mini-dictionary to the full-blown window, you can make even a "normal" lookup use this style -- just go into Dictionary's Preferences and set the Contextual Menu button to "Open Dictionary panel." Just for fun, I made a short movie of the rapid-fire lookup feature. If you're not running 10.4, you'll still need QuickTime 7 to view it, as I used the H.264 codec to encode it.]