In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included Levels of Evidence and expert clinical support. This section on "Pharmacotherapy" is one of 5 guideline articles. Despite emerging data on efficacy and tolerability differences amongst newer antidepressants, variability in patient response precludes identification of specific first choice medications for all patients. All second-generation antidepressants have Level 1 evidence to support efficacy and tolerability and most are considered first-line treatments for MDD. First-generation tricyclic and monoamine oxidase inhibitor antidepressants are not the focus of these guidelines but generally are considered second- or third-line treatments. For inadequate or incomplete response, there is Level 1 evidence for switching strategies and for add-on strategies including lithium and atypical antipsychotics. Most of the evidence is based on trials for registration and may not reflect real-world effectiveness. Second-generation antidepressants are safe, effective and well tolerated treatments for MDD in adults. Evidence-based switching and add-on strategies can be used to optimize response in MDD that is inadequately responsive to monotherapy.