Depression is one of the most common mental health problems encountered in primary care and a leading cause of disability worldwide. In many cases, depression is a chronic or recurring disease, and as such, it is best managed like a chronic illness. Moreover, medically ill patients with depressive disorder are at greater risk for a chronic course of depression or less complete recovery. Antidepressant medications and psychotherapies can help many if not most depressed individuals, but millions of primary care patients do not receive effective treatment. Effective management of depression in the primary care setting requires a systematic, population-based approach which entails systematic case finding and diagnosis, patient engagement and education, use of evidence-based treatments including medications and / or psychotherapy, close follow-up to make sure patients are improving and a commitment to keep adjusting treatments or consult with mental health specialists until depression is significantly improved. Programs in which primary care providers and mental health specialists collaborate effectively using principles of measurement-based stepped care and treatment to target can substantially improve patients’ health and functioning while reducing overall health care costs.