1) Delete first thing every morning.
When I open my inbox each day I delete unnecessary mail and customarily for me this includes all forwards. I just don't have time for them. If I receive e-mails from lists I never signed up to be on and don't want to be on, I take a moment to unsubscribe, knowing it will save me time on other mornings to not have to keep deleting that piece of mail. (I do not delete myself from all lists - if friends have put me on certain valuable things as a courtesy, I stay on them.) Upon occasion I do get questioned by people who say things like, "Did you get the forward I sent you about the supernatural frog from Mexico that healed people as it hopped by?" and I say, "you know, being that I get a few hundred e-mails a day it's kind of hard for me to keep up with ones like that." Usually people understand.
2) Only touch each piece of mail once.
I leave it sitting in my box throughout the day (unopened) until I am ready to answer it. If I don't have time to answer it right then I don't open it. I touch mail once, whether it's by email or U.S. Mail. I don't have time to keep going back to sort through what I have and haven't answered. So, I open it, answer it, and am done with it. The only exception to this is the rare e-mail that might be a difficult one requiring some prayer or thoughtful response beyond the norm.
3) Put responses requiring more time on to-do list, and get them out of the inbox.
If a response takes more time and prayer, I try to answer the person right then saying that their e-mail is under consideration and I'll get back to them asap. Then I put the response on my to-do list so I don't forget it.
4) Don't carry e-mail over til' the next day.
I answer it all within 24 hours if possible. If it piles up from day to day it just feels too overwhelming.
5) Only answer things that truly need a response
If someone writes me a direct email, requesting a response, I always answer it. If they just want me to read something to be aware of it, I don't necessary comment on it. If they ask for a direct answer on something that's just an FYI type thing I might write back and simply thank them in one sentence for keeping me in the loop.
Hope this helps those of you who have overflowing in-boxes!