Your users will always be able to unsubscribe from your emails using the button that is located at the bottom of the email. But for users who reply to you asking to be removed, the suppression list is the best approach.
1. Within the product portal go to Marketing>Suppression List.
The marketing icon looks like this:
2. From there you will be presented with a list containing all of your opt-outs. You can search for contacts within the list to verify they have been added in.
3. To add a new user, click on Suppress User on the top right side of your page. All you need to do is type in the email, this will add the user to the suppression list.
4. It's important to note that if you are making SMS campaigns, you need to make sure to toggle the Receive SMS button that is in each row of contacts.
It will look like this:
5. Lastly, you can completely delete a user from your site history by using the trash can icon on the right side of their profile. It will look like this: