Behavioral treatments arranging differential reinforcement effectively treat severe problem behavior while interventions are underway. However, many events challenge these treatments clinically, thereby producing relapse of problem behavior. This paper reviews six laboratory models of treatment relapse for their relevance to understanding the processes underlying treatment relapse, including resurgence, reinstatement, rapid reacquisition, disinhibition, and spontaneous recovery. In addition, we also discuss clinical examples resembling these models and accompanying effects, as well as studies examining the combined effects of these laboratory models. Finally, we describe approaches developed in laboratory studies to mitigate treatment relapse using a variety of approaches involving both antecedent and consequence-based interventions. This research provides a foundation from which basic and clinical researchers can collaborate to establish more durable treatments for problem behavior. (PsycINFO Database Record (c) 2018 APA, all rights reserved)