I just went through my email inbox and nuked over 4500 messages. All since January 2005. Anything important is either archived as a project file, or available through the magical wondrousnes of The Goog.
I'd been letting messages just stay in my inbox, using Spotlight and Smart Folders to find stuff easily, but over the last few days the U of C's webmail client has been warning me (via a friendly BLINKING RED MESSAGE) that inboxes with over 5000 messages are bad, 'mkay? So, I took the hint and nuked all kinds of stuff. Everything from "status update - February 2005" to various random ping messages.
I don't think I've trashed anything critical, but should be able to focus a little better on a smaller inbox now. I couldn't quite get to the Getting Things Done empty inbox state, but it's an order of magnitude closer.