Depressive Disorders in the DSM‐5 include Major Depressive Disorder, Persistent Depressive Disorder, Disruptive Mood Dysregulation Disorder, and Premenstrual Dysphoric Disorder, along with unspecified and secondary depressive conditions. This chapter mostly focuses on practical considerations in pharmacotherapy. It also focuses on topics of clinical importance when using conventional antidepressants to treat major depressive disorder: efficacy, overdose potential, treatment‐emergent suicidality, therapeutic monitoring and drug–drug interactions, discontinuation syndromes, side effects and adverse events. Major psychological issues that arise in the treatment of depression are also discussed here. Successful treatment of depression is a collaborative effort involving patient, family, clinician (and associates). Faith is needed, and so persuasion and the support of others surrounding the patient can have greater influence on treatment outcome than does the particular choice of pharmaceuticals or psychotherapeutic method.