In 2000, the economic burden of depression in the United States was estimated to be $83.1 billion. Although many effective treatments are available and treatment rates have increased, response and remission rates for patients with depression remain low and multiple treatment trials are often required. Whether patients are adherent to their medication affects response and remission rates, and nonadherence is common among patients with depression. Increasing adherence improves treatment outcomes and lowers treatment costs. Interventions that increase adherence include educational, behavioral, affective, and provider-targeted strategies; transdermal delivery of drugs also may increase adherence by simplifying the patient's medication regimen. While monoamine oxidase inhibitors (MAOIs) have proven efficacy for depression, particularly for patients with treatment-resistant or atypical depression, they are underprescribed due, in part, to concerns over dietary and drug restrictions that are required to avoid potential serious side effects. However, newer MAOI formulations, including a transdermal delivery system, have improved safety and tolerability profiles and avoid or lessen the need for dietary restrictions, giving clinicians another option for treating patients who may be nonadherent or nonresponsive to their current antidepressant.