Depression is a common and potentially disabling condition. Treatment, especially when applied assertively, can improve outcome and result in symptom remission in many cases. However, treatment non-adherence is common and a major contributor to non-response. A variety of factors can contribute to premature discontinuation. For example, side effects may lead to a patient stopping use of a medication. However, a common and often overlooked cause is lack of therapeutic response, which may be the result of prescribing behaviors. Other factors include attitudes of patients, families, or clinicians themselves. Assertive treatment, active side-effect management, and appropriate patient and family education may increase the likelihood of treatment continuation to remission.