If you assign actions to the "Global Mapping“ table, these actions are executed for *every* press of the buttons you assigned them to.

If you assigned Plex-specific actions to the buttons of your remote in the "Global Mapping“ table and Plex is not running, Remote Buddy will execute these actions regardless of what application you run or don’t run. If you only assigned Plex-specific actions and Plex is not running, Remote Buddy will still send UDP packages containing the commands on every button press. However, if Plex is not running at the time, it can't receive or react to them and you won’t see any reaction.

If you want to use more than one application (which I assume you want), you shouldn’t use the Global Mapping table at all, but leave it at its default settings. The correct place to change the actions associated to a button on a per-application basis are the application-specific mapping tables (for Plex that’s Remote Buddy Preferences > Mapping > Plex).

For more information please see the included help - or the online copy of the included help at 
http://helpbooks.iospirit.net/remotebuddy/english/ref_prefs_mapping.html

Best regards, 
Felix Schwarz