Currently, pharmacotherapy is the primary treatment modality for depression. Various classes of antidepressants have been developed and are widely used at present. Although the antidepressant effects of these drugs are thought to be similar, there are numerous differences between drugs in pharmacologic characteristics, side effects, and tolerabilities. Furthermore, 40~50% of patients may not respond sufficiently to the first-line antidepressants they take. As the response rates are substantially insufficient, and the side effects are not uncommon, the optimal treatment of antidepressants is somewhat difficult. Therefore, the clinicians treating depression should understand the characteristics of various antidepressants and also the optimal treatment strategy. In this review, we introduce various antidepressants and optimal treatment strategies for the treatment of depression.