Although antidepressants are effective, no more than one third of the depressed patients who begin treatment achieve full remission within 8 weeks of therapy. Remission, defined as virtually complete relief of symptoms and return to full functioning in all areas of life, should be thought of as the optimal goal for the initial phase of treatment of depression. This goal is recommended because residual symptoms (i.e., response without remission) are associated with a myriad of risks, including a higher rate of relapse. When compared with monotherapy, selective serotonin reuptake inhibitor (i.e., the current first-line standard of care) strategies may improve remission rates. These strategies include using maximally tolerated (i.e., higher than usual) doses of medication, switching to an antidepressant thought to have more than one mechanism of action, combining dissimilar medications (to presumably treat a broader range of symptoms), and using a combination of psychotherapy and medication. Ensuring that patients are indeed adherent with treatment is also worthwhile before assuming that a treatment has failed.