You can use ladders to attempt to re-activate dormant activists on your list who haven't engaged with your email for a long time, and unsubscribing them after a final attempt to preserve deliverability. (It's good practice to only email people on your list who are active -- emailing many people who are inactive can be a flag email providers like Gmail use to determine if your email should go to spam boxes or not.)
The ladder's trigger would be "Received Any Email", so any activist who receives an email from you will enter the ladder.
The next step would be to wait a long period of time, perhaps 90 or 180 days.
Then, a decision step would be added, with the query has this activists opened an email in the last 90 or 180 days, or has this activists clicked an email in the last 90 or 180 days.
If yes, no further steps, they are active and they exit the ladder, only to be put back in when they receive the next email and wait again.
If no, a send an email action step would be added, sending them a re-activate email trying to get them to engage. For example, you could warn activists that they will be unsubscribed unless they open the email, or you could offer them something special in an attempt to get them to engage with the email.
After that, another wait step could be added, for 7 days, with another decision again seeing if the activists opened or clicked an email in the last 90 or 180 days.
After that, on the no branch, another re-activate email and wait.
And finally, after another decision looking for activity, on the no branch, an action to unsubscribe the activist.
The effect of this entire rung is that each activist enters when receiving email from your group, and they wait for 3-6 months, after which they are evaluated to see if they opened or clicked any of your email in the last 3-6 months. If not, they are sent emails asking them to re-engage and are tested again to see if they engaged with those emails. If they continue to not respond to these emails, they are finally unsubscribed.
Here is a screenshot of this example, taken from the ladder's edit page. Click to open up the image directly for a larger view.