Depression affects an estimated 8% of persons in the United States and accounts for more than $210 billion in health care costs annually. The U.S. Preventive Services Task Force (USPSTF) and American Academy of Family Physicians recommend screening for depression in the general adult population. Additionally, the USPSTF recommends screening children and adolescents 12 to 18 years of age for major depressive disorder. All screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up. The two-item and nine-item Patient Health Questionnaires (PHQs) are commonly used validated screening tools. The PHQ-2 has sensitivity comparable with the PHQ-9 in most populations; however, the specificity of the PHQ-9 ranges from 91% to 94%, compared with 78% to 92% for the PHQ-2. If the PHQ-2 is positive for depression, the PHQ-9 or a clinical interview should be administered. Screening all postpartum women for depression is recommended by the USPSTF, American Academy of Family Physicians, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists. Women should be screened for depression at least once during the perinatal period using the PHQ-2, PHQ-9, or Edinburgh Postnatal Depression Scale. In older adults, the Geriatric Depression Scale is also an appropriate screening tool for depression. If screening is positive for possible depression, the diagnosis should be confirmed using Diagnostic and Statistical Manual of Mental Disorders, 5th ed., criteria.