Mental and somatic illnesses have historically been treated as separate domains. It is increasingly apparent, however, that disorders of the mind arise directly from disorders of the brain. This insight raises the difficult problem of identifying the biological mechanisms of psychiatric disease and of using this knowledge to develop better diagnostic frameworks and treatments. In this chapter, we explore evidence that psychiatric disorders considered distinct in our current diagnostic scheme derive from shared or overlapping underlying biological abnormalities. To illustrate biological commonalities among different disorders, we describe data from cognitive neuroscience, which has produced evidence for similar brain systems involved in multiple, often disparate, psychiatric conditions. We primarily explore four neural systems in illustrating these points—ventral striatum, dorsal striatum, dorsolateral prefrontal cortex, and anterior cingulate cortex. In each case, considering a region's normal functions helps better make sense of its dysfunction in particular psychiatric conditions. Such an appreciation contributes to an understanding of which clinical aspects of particular disorders reflect shared neurobiological underpinnings.