The relationship between depression and anxiety disorders has long been a matter of controversy. The overlap of symptoms associated with these disorders makes diagnosis, research, and treatment particularly difficult. Recent evidence suggests genetic and neurobiologic similarities between depressive and anxiety disorders. Comorbid depression and anxiety are highly prevalent conditions. Patients with panic disorder, generalized anxiety disorder, social phobia, and other anxiety disorders are also frequently clinically depressed. Approximately 85% of patients with depression also experience significant symptoms of anxiety. Similarly, comorbid depression occurs in up to 90% of patients with anxiety disorders. Patients with comorbid disorders do not respond as well to therapy, have a more protracted course of illness, and experience less positive treatment outcomes. One key to successful treatment of patients with mixed depressive and anxiety disorders is early recognition of comorbid conditions. Antidepressant medications, including the selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors, are highly effective in the management of comorbid depression and anxiety. The high rates of comorbid depression and anxiety argue for well-designed treatment studies in these populations.