Treatment-resistant depression (TRD) is a major public health problem in terms of its prevalence and in terms of individual suffering and cost to society. Best estimates indicate 12-month prevalence rates of approximately 3% for Stage 1 TRD (failure to respond to 1 adequate trial of an antidepressant) and approximately 2% for Stage 2 TRD (failure to respond to 2 adequate trials). The current article provides a brief review of the definitions, prevalence, and various treatment options for TRD, including switching, augmentation, and combination therapies and use of nonpharmacologic treatments. Given the public health importance of TRD, the relative absence of adequately powered, double-blind trials is striking.