* To reload a page and bypass the cache:
o for version 4 and newer:
o Hold down the Shift key and click the Reload toolbar button.
o for version 3 and older:
o Hold down the Command key, and press R. This kind of "regular" reload will usually bypass the cache.
o Note that Apple ([1]) claims that clicking the Reload toolbar button has the same effect as Command-R, but this is not true; frequently the button will not bypass the cache. In fact, numerous Web developers have reported erratic behavior in general in bypassing the cache in Safari, in some cases having to resort to both clearing the cache (see below) and then quitting and relaunching the application.
* To completely clear the cache (see note above):
o From the 'Safari' menu, choose 'Empty Cache...' or hold down the Option and Command keys and press E.
* To disable the cache permanently (this method only works on old versions of Safari 2 on OS X 10.4 and previous versions, and is not recommended as it may potentially (although rarely) cause system instability):
o Quit Safari by choosing 'Quit' from the 'Safari' menu, or by holding down the Command key and pressing Q.
o Open a Terminal window by double-clicking 'Terminal' within the 'Utilities' folder, which is within the 'Applications' folder.
o Type the following commands, which are case-sensitive, each followed by the Enter key:
+ rm -rf ~/Library/Caches/Safari
+ touch ~/Library/Caches/Safari
o Quit Terminal by choosing 'Quit' from the 'Terminal' menu, or by holding down the Command key and pressing Q.
o Relaunch Safari.
* To disable the cache for the session (Requires developer menu to be enabled. Go to Preferences, pick the Advanced Tab, then click "Show Develop menu in menu bar"):
o Click Develop, then click Disable Caches
From: http://en.wikipedia.org/wiki/Wikipedia:Bypass_your_cache
tell application "System Events" to tell process "Safari" to button 1 of text field 1 of splitter group 1 of group 1 of tool bar 1 of window 1. AFAIK there's no way to emulate pressing it while modifier keys (or ⇧) though. – Lri Jul 29 '11 at 13:11