I ignore those that indicate vacation, conference, tradeshow or other legit out of office situation.
We take appropriate action to suspend/unsubscribe those that indicate the person has left the company, retired, passed away, etc. We don't want to resend any email to accounts where we've been given the indication that the person is gone, as that's a possible trigger to blacklist us--not only for that person, but the entire organization. Sometimes these email addresses are turned into spam traps, so you don't want to continue to send mail once you receive notice the person is gone.
Sometimes we get the notice from a central mail server (mailadmin@companyX.com). That requires some manual review of the campaign to determine who we mailed at Company X to analyze who we should take out of our mailing rotation.
I've also encountered email forwarding to people who are no longer at their firm. Our send list includes JohnDoe@CompanyX.com, but we'll get a response that says JaneSmith@CompanyX.com is no longer with the firm. It probably makes sense to at least suspend John's email address for a while.
There are different schools of thought on what to do with the referral names included in responses--where the autoreponse says John Doe is no longer with the firm. Direct inquiries to Jane Smith. Obviously, Jane hasn't opted in, so you don't want to just add her to your lead database. You might try sending a personalized message that mentions that you received the autoresponse from JohnDoe who had opted in for your mailings, and was wondering if Jane might like to subscribe as well.
We don't have a huge number of these messages, so we process manually.
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