Over on the EEC blog Dan Babb and Austin Bliss share some strategies to re-engage inactive subscribers:

Explore segmentation tactics.
One-to-one communication and segmentation are so easy to do with email. It’s highly recommended that you start categorizing your non-responders into various cells, and start testing different content and subject lines for each cell. When you identify a strategy that starts to show positive results (getting people engaged), use that strategy for the remainder of the cells.

Consider a survey.
Inviting subscribers to participate in a survey can be an effective tool for re-activation programs. Ask your subscribers for information that can be helpful in providing them content and offers they will find valuable.

Get a new email address.
Is the fact that the subscriber is not responding a sign that the email address is going to be invalid soon (abandoned email account)? Should you try to find a new email address for that subscriber? Over the last 6 to 8 months, there’s been an increase in the number of customers that are submitting their “chronic non-responders” for email change of address and email update services. One reason for this trend is because of slowing list growth. As a marketer’s growth rate of their opt-in house file slows down, the loss of emails due to bounces and non-responders start to really show their impact in terms of lost revenue. Therefore, finding a new email address for a non-responder has been a strategy that’s being adopted by more companies.

Is there a risk if you continue to email non-responders?
This question came up. The general consensus was that there probably is not a risk that the non-responder will press the automated complaint buttons or report you as spam. However, abandoned emails do sometimes get converted to “honeypots” or “spam traps” by the ISPs. The ISPs don’t tell us good guys which addresses may have triggered a spam trap, so you don’t know which ones to remove from your list. A suggestion: do a 1-year purge—anyone who hasn’t shown any action (as defined above) could be suppressed from future campaigns.

Source: Email Experience  Blog