Much controversy has surrounded the diagnosis of bipolar disorder (BD) in children and adolescents. However, recent work from an affective neuroscience perspective has advanced what is known about the boundaries of emotion regulation in BD compared to typically developing youth. In this article, we first briefly review the clinical issues that have contributed to this diagnostic controversy. Second, we discuss our phenotyping system, which can be used to guide neurobiological research designed to address these controversial issues. Third, we review what is known about the fundamentals of emotion regulation in human and nonhuman primate models. Fourth, we present recent data demonstrating how children and adolescents with BD differ from those without psychopathology on measures of emotion regulation. Taken as a whole, this work implicates a neural circuit encompassing the prefrontal cortex, amygdala, and striatum in the pathophysiology of pediatric BD.