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Major depression (MD) is the most common psychiatric disorder after traumatic brain injury (TBI). Yet, diagnosing MD is often challenging because of cognitive, emotional, and somatic symptoms that overlap with TBI and other psychiatric disorders. Best current evidence suggests that depressed mood is characterized more by irritability, anger, and aggression than by sadness and tearfulness in persons with TBI. Rumination, self-criticism, and guilt may best differentiate depressed persons from nondepressed persons. Anxiety, aggression, sleep problems, alcohol use, lower-income levels, and poor social functioning appear to be primary associated factors to MD. Objective levels of injury severity, impairment, and functioning do not appear to be related to developing MD. The presence of “organic” TBI sequelae that overlap with the Diagnostic and Statistical Manual of Mental Disorders–Version IV MD criteria does not …