1. Most often used to force quit recalcitrant programs--will often work when neither the Dock nor the Apple menu Force Quit nor the key combo version will do the job. The item that is not responding has a notice to that effect, in RED, in the Activity Monitor list. Click the red Stop icon in the tool bar, then the click the Force Quit button in the drop down sheet. It can also be used to Quit processes that you otherwise can't see running, such as the Dock, SystemUIServer, and any number of others.
2. You can check what applications are using how much of your CPU, and see if one of them is being a real hog, which can slow down everything else. Make sure All Processes are showing in the drop down menu, then click the %CPU column header. If a program you aren't actively using, or one that normally behaves itself, is hogging the CPU you can quit the program and then relaunch it later. It could have been temporary glitch and things will return to normal. Make sure the program in question is one that belongs to you!
3. Same deal in RAM use. Click the Real column header to see how much RAM is being used. Safari's RAM use tends to creep ever upward. If you notice it has gotten really piggy quit it and relaunch it later when you need it. You can also click the System Memory tab at the bottom of the window to see a handy pie chart and a list of RAM use. If you have Free RAM (a vibrant green in the pie chart) all is fine. Don't worry about the Inactive RAM (blue), the system can assign this RAM to other uses if necessary. But if the pie chart has no green and only a little blue, then you need to quit some programs, especially if you see the Page ins/outs have a lot of the "outs" listed: your system is writing RAM contents to disk which slows things WAY down. While running fewer programs will help, and running RAM hogs only when you actually have to use them will also help, the only real solution is more RAM. For an excellant summary of RAM use and the meaning of page ins/outs, see THIS discussion at MacOSX.com, especially the post by perfessor101.
4. One interesting--and sometimes helpful--thing you can do is select an application and then click the Inspect item in the toolbar. A new window opens with all sorts of information about that application. If you click the "Open Files and Ports" tab you can see all the things that the program is using to run. This can sometimes help you figure out possible problems. For instance, before cleaning out all your caches, you might look and see just which caches a problem application is actually using. Further, if you click on the Sample button you can get a picture of just what an application is doing. Some people have actually managed to diagnose a problem this way: for instance discovering that Photoshop is repeatedly trying to contact a network server that is disconnected, or trying to access a printer that is non-functional.