We describe the functioning and well-being of patients with depression, relative to patients with chronic medical conditions or no chronic conditions. Data are from 11 242 outpatients in three health care provision systems in three US sites. Patients with either current depressive disorder or depressive symptoms in the absence of disorder tended to have worse physical, social, and role functioning, worse perceived current health, and greater bodily pain than did patients with no chronic conditions. The poor functioning uniquely associated with depressive symptoms, with or without depressive disorder, was comparable with or worse than that uniquely associated with eight major chronic medical conditions. For example, the unique association of days in bed with depressive symptoms was significantly greater than the comparable association with hypertension, diabetes, and arthritis. Depression and chronic medical conditions had unique and additive effects on patient functioning.