Depression is a common clinical problem seen in primary care. Despite a high prevalence of depression in patients of all ages, it is underdiagnosed and undertreated by primary care and other nonpsychiatric health care providers—the practitioners most likely to see the patient initially, greater than 50% of the time. Differentiating depression and physical illness is difficult and often comorbidlty confounds, the problem. Diagnostic criteria for depression are presented along with tips for assessment of suicide risk. Laboratory screening should be done as part of the diagnostic process to document certain changes in physiological parameters related to depression. The choice of treatment for depression includes psychotherapy, medication, ECT, or combined treatment with medication and psychotherapy. The result of managed care is that primary providers are more often responsible for medication management of depression than they were in the past. An overview of antidepressant pharmacotherapeutics for primary care is presented.