As descriptors for the clinical course and treatment of depressive illness, terms such as response, remission, and recovery have evolved with our understanding of the disease, yet have been inconsistently applied as measures of outcome in clinical trials. Indeed, a wide variety of definitions may be found in contemporary study reports. This article reviews the breadth of definitions, the ways in which they affect interpretation of clinical study data, and their relationship to clinical practice. Therapeutic experience over the past decade indicates that remission is the optimal outcome of treatment, and patients said to have remitted generally are considered to be well. By some standards, however, patients may be considered in remission despite harboring one or two minor symptoms. The presence of residual symptoms, like continued functional or social impairment, is considered a strong predictor of relapse or recurrence. Wellness thus must be determined by symptom level, functional status, and increasingly (as our understanding of brain neurophysiology grows), the nature of pathophysiologic changes. The various factors that may predispose patients toward or away from a state of sustained recovery also are reviewed, helping to inform a concept of remission more consistent with true wellness. Defining such a target can serve to sharpen the focus of therapeutic intervention in the clinical environment. This dynamic is reinforced via the integration of current best therapeutic thinking in research settings, leading to clinical trials that more closely approximate an ideal, remission-focused treatment regimen.