Major depressive disorder (MDD) is defined as five or more of the following symptoms in the past 2 weeks, during which at least one is depressed mood or loss of interest or pleasure: depressed mood; diminished interest or pleasure in activities; significant weight loss or gain, or decreased or increased appetite; insomnia or hypersomnia; psychomotor agitation or retardation; fatigue or loss of energy; feelings of worthlessness or excessive or inappropriate guilt; poor concentration or indecisiveness; or recurrent thoughts of death or suicidal ideation, plan, or attempt. Screening for MDD is recommended in the general adult population when resources are available for diagnosis, management, and follow-up. Several screening tools are available, including the Patient Health Questionnaire-9 (PHQ-9) and Beck Depression Inventory for Primary Care (BDI-PC). Laboratory tests may be considered to assess for significant comorbidities, differential diagnoses, or contraindications to treatment. Management of MDD depends on its severity and may include psychotherapy, pharmacotherapy, or both. The drugs most commonly used are selective serotonin reuptake inhibitors. Treatment should be continued for at least 16 to 24 weeks to prevent recurrence. Referral to a psychiatrist or other mental health clinician should be considered when the diagnosis is in question or when symptoms do not improve with standard treatment.