There is a gear in the bottom right hand corner of the developer tools called settings that allows you to disable the cache.
On the pc you can open that by pressing ctrl+shift+i
or on the mac command+option+i
Since Chrome 19 the setting is now in General.
There is now a shortcut on the Network panel as well.
network panel shortcut http://i.imgur.com/NuATTPq.png
A recent tweet from ChromiumDev states
Chrome DevTools' Disable Cache invalidates the disk cache (great for developing!), but.. only while devtools is visible.