Individuals with major depressive disorder (MDD) have high rates of disability, morbidity, and mortality, and are responsible for as many as one-fourth of all healthcare visits. Within primary care settings, 5% to 10% of adults have MDD, but only one-third of those are diagnosed. Thus, despite the devastating decrease in the quality-of-life and productivity of patients, depression is often under-diagnosed and therefore inadequately treated. Most patients with depression who are adherent with their treatment plan still experience residual symptoms, and require lon-term treatment. Adequately managing residual symptoms will hopefully lead to increased remission in these patients. This supplement focuses on the different types of residual symptoms that patients experience and suggests various treatment options.