The high likelihood of a chronic course of depression underscores the need to identify at intake patients most at risk for long-term nonremission. In a naturalistic study of 313 unipolar depressed patients, potential symptom-based risk factors were assessed at treatment intake and were used to predict a chronic course of treated depression over a 10-year interval. The prototypic chronically depressed patient was an individual who at baseline experienced more severe symptoms of fatigue, loss of interest in usual activities, trouble sleeping, and thoughts about death or suicide; was not calm, successful, or self-confident; and did not socialize with friends outside the home, and frequently coped with stressors by avoiding other people. A larger number of risk factors was associated with a higher likelihood of experiencing a chronic course. High-risk patients who received more psychological treatment during the index episode were more likely to experience a long-term course of remission or partial remission.