ABSTRACT-Clinical depression is a significant mental health problem that is associated with personal suffering and impaired functioning. These effects underscore the continuing need for new approaches that can inform researchers and clinicians when designing interventions. The present article proposes that individual differences in the self-regulation of sadness and distress provide an important link between stress, depressed mood, and the onset of depressive disorder, and that a better understanding of the ways children successfully manage dysphoric emotions will lead to improved prevention and treatment of pediatric depression. After examining the normative development of responses that children use to attenuate sadness, aspects of the neurobiological infrastructure that both enable and constrain such selfregulatory efforts, and affect regulation of children at familial risk for depressive disorders, this article concludes by calling for integrated, developmental, multidisciplinary studies of sadness self-regulation