This chapter reviews the phenomenology and neurobiology of co-occurring anxious and depressive symptoms and disorders, and describes their clinical relevance, including prognostic and treatment implications. Several demographic factors were also associated with anxious depression, including African-American or Hispanic race, and lower educational attainment or income. It examines the extent to which genetic factors contributing to anxiety and depression are shared by reviewing family, twin, and molecular association studies. A unique series of twin studies has examined the genetic contribution to the comorbidity of major depressive disorder (MDD) and generalized anxiety disorder (GAD). The evidence from multiple lines of inquiry suggests that there is a biologic relationship between anxiety and depression, including a shared genetic diathesis that may manifest in either a depression or an anxiety phenotype. Brain imaging studies suggest that comorbid anxiety and depression may exhibit some additive effects of the pathophysiology of individual depression and anxiety disorders.