Depressive disorders are far more serious than most people realize, and depressive disorders are disabling affected persons progressively earlier in life. Heavy utilization of medical services, extensive disability and morbidity, and high suicide risk exact a staggering economic toll in the United States annually. Depressive illness is, like pneumonia and septic shock, a dread complication of major medical illness, and depressive illness appears more frequently as the medical illness worsens; diseases affecting the brain may have the highest rates of depressive symptoms. Correctly diagnosing a depressive disorder in a medically ill patient is a clinical challenge that requires systematic, persistent clinical scrutiny. Compassion demands that depressive disorders, when diagnosed, be treated aggressively.