That genes influence how we feel and behave is without question. Yet despite decades of research, the mechanisms through which this occurs are only recently coming into focus. This chapter reviews studies that have contributed toward narrowing the gap in knowledge regarding genes and emotional behavior. First, the discussion focuses on Williams syndrome, a genetic “lesional” model, which offers an exceptional framework for understanding the relationship between genes, brain circuits, and atypical socioemotional behavior. The chapter then reviews recent findings for the more common case of mood disorders, for which as for most psychiatry conditions the genetics are complex. The concepts of intermediate phenotypes and imaging genetics will be introduced here as tools to address this question. Finally, evidence at the neurochemical level is presented which suggests that prosocial neuropeptides play a crucial role in the neurobiological chain linking genes and emotion.