Why are some mailings and being sent to contacts who have opted out of receiving emails? 

Environment:

Audiences, Global Opt-in

Resolution:

When defining an audience segment, the system-defined global opt-in field is not automatically included as a filter in the segment.

However, when configuring your mailing, there are several options on the Audiences tab. Within a mailing, in the Options section of the Audiences tab, the system defaults to honor both the global opt-in and the external suppression list.  As a result, with the checkboxes enabled on the Audience tab, the mailing does not get sent to contacts whose global opt-in is set to No or if their email address is included on the global suppression list.

Since the mailing allows you to exclude contacts based on the global opt-in and external suppression list, you do not need to add filters for these features when you define your segment.

If you have custom opt-in fields to opt contacts in to specific types of mailings, include a filter for the appropriate opt-in field when you define your audience segment.