Now that chx has beaten me to it, I'm going to profile and patch and find all the low hanging fruit to cache in drupal. Here's an improvement to the module_hook function.

A few weeks ago, I was brought in to help raise the performance of a site running tiki that was under high load.
I saw Rasmus Lerdorf give a very interesting talk on PHP optimization called "Getting Rich with PHP5." In it, he recommends the use of valgrind as a way of holistically profiling a web server running an application. That's a nice way of seeing what's holding you down when you have that luxury, but what can you do when the machine is under heavy load?