Anhedonia, the reduced ability to experience pleasure, has been critically implicated in a wide range of adolescent mental disorders and suicidal behaviors.1,2 Presently, medication as well as most first-line psychotherapeutic approaches do not sufficiently address motivational and reward-processing deficits that characterize anhedonia, and thus, treatment failure is common. To overcome limitations of a categorical nosologic system and improve treatments for core dysfunction, the National Institute of Mental Health’s Research Domain Criteria initiative provides a framework for research focusing on core domains of functioning, such as the Positive Valence Systems. Through this lens, research has sought to clarify the neural circuity underlying anhedonia and, in doing so, provide a framework to elucidate how and why anhedonia leads to adverse mental health outcomes across the lifespan.