Persistence in and timely disengagement from personal goals are core components of successful self-regulation and therefore relevant to well-being and performance. In the history of motivation psychology, there has been a clear emphasis on persistence. Only recently have researchers become interested in goal disengagement, as mirrored by the amount of pertinent research. In this review, we present an overview of the most influential motivational theories on persistence and disengagement that address situational and personal determinants, cognitive and affective mechanisms, and consequences for well-being, health, and performance. Some of these theories use a general approach, whereas others focus on individual differences. The theories presented incorporate classical expectancy-value constructs as well as contemporary volitional concepts of self-regulation. Many of the theoretical approaches have spread to applied fields (e.g., education, work, health). Despite numerous important insights into persistence and disengagement, we also identify several unresolved research questions. Expected final online publication date for the Annual Review of Psychology, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.