Depression is a complex and heterogeneous disorder whose cause is poorly understood. Theories on the mechanisms of the disease have often focused on either its neurobiology or its cognitive and behavioral manifestations. Recently, studies exploring how depressed patients process reward and punishment have linked these two facets together. It has been suggested that individuals with a dysfunction in a specialized network of brain regions are unable to exploit affective information to guide behavior. Deficits in this ability might predispose such individuals to develop depression, whereas subsequent restoration of this ability--whether through pharmacological or behavioral treatments--might enable recovery from the disorder. Here we review behavioral, neuroimaging, and computational findings relevant to this hypothesis. There is good evidence that depressed patients exhibit abnormal behavioral responses to rewards and punishments and that these tendencies correspond to aberrant function in frontostriatal systems modulated by the monoamine systems. Furthermore, computational studies have generated testable predictions for how these neural signaling and neurochemical abnormalities might contribute to the symptoms of depression. Combining these approaches--as well as molecular and behavioral work in animals--provides great promise for furthering our understanding of this common and debilitating disease.