Although remission is recognized as the optimal outcome of treatment for depression, remission lacks a universally accepted definition. This is partly due to the lack of objective biologic markers or tests that confirm a response to treatment and no well-defined end points of treatment. Significant symptoms may still exist even though patients may have a full response as measured by currently available standardized psychiatric rating scales. In addition, many patients may experience marked improvement in depressive symptoms but still have impaired psychosocial and work function. Wellness should be determined by evaluating a combination of three key domains: symptoms, functional status and pathophysiologic changes. In choosing an initial medication for depression, physicians are often guided by a mix of evidence-based medicine and unvalidated or even inaccurate clinical lore. In general, most available agents have comparable effectiveness; however, the subtype of depression and age of the patient should be considered.