I have had my personal email address / domain for over 10 years now and with that I get a lot of spam being thrown at it. Upon a recent check, I get over 800 spam emails per day.
Almost all of the spam I get comes from forged email addresses or non-existent email addresses. Using this key part of the equation, an open-source software project called TMDA (tagged message delivery agent), will challenge any unrecognized email senders with a simple reply asking them to verify their email address. If the email sender is forged, then the spammer will never get the challenge and I will never see the email. If the sender is legit and the message contains spam, I will threaten litigation (I have a legit contact now) with my state's spam email laws. If the sender is not selling me something, then I get the email as is and their name is entered into a future whitelist.
TMDA manages all of this interaction at the email server level, so it is client agnostic and I never need to see spam email again. You can obtain more information about this software at the following url: http://tmda.net/