At CIIN we have gotten more and more unwanted/crap/malicious e-mail to the point that we have had to activate an anti-spam program called BoxTrapper. As a practical matter, that means messages sent to us will probably get an automated message requiring the sender to simply hit "reply" in order to prove the message comes from a person and not a program.
It is an inconvenience, but once the person replies to the automated message, their original message goes through — no further action needed. Also, this a one-time thing. The sender should not have to do this again unless they send from a different account.
By the way, this has dramatically cut down on the junk e-mails we get.
This brings up a point to consider, do not just assume that your e-mails get to their destination. BoxTrapper is one of many anti-spam programs out there. Some are better and more convenient than others. If a message is important and you get no response, follow up in some way. There are too many ways an e-mail can go astray.