This chapter discusses depression in the context of alcoholism and other substance-use disorders. Independent depression syndrome describes a patient who meets criteria for major depression or dysthymia, and it is clear in the history that the depression is independent of effects of substances. The Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) introduced substance-induced depression to recognize the existence of syndromes of depression that cannot be established to be independent, but that nonetheless appear to exceed the usual effects of substance intoxication or withdrawal and require clinical attention. A number of other psychiatric disorders e.g. bipolar disorder, ADHD, PTSD, and some other anxiety disorders, antisocial and borderline personality, co-occur with substance-use disorders and may account for some of the association between depression and substance abuse. Chronic medical disorders, especially those producing chronic pain, also need to be considered.