Can traumatic life events cause depression? Studies generally point to a connection between adverse life events and depression. However, establishing a causal, rather than associative, connection is more problematic. The authors structure this examination of the question around three major themes: the pathophysiological role of stress in depression; whether or not a subtype of depression exists that is particularly stress-inducible; and, finally, how best to diagnose and treat depression in relation to its biological basis.