The history of studying the effectiveness of therapy of patients with depression by irreversible non-selective monoamine oxidase inhibitors (MAOIs) is analyzed and systematized. Authors describe the stages of the appearance of the first data on the effectiveness of treatment by the first representatives (the 50^s of the XX century), the targeted study of the effectiveness of the use of numerous «new» representatives and the emergence of disagreements in assessing the power of therapy (the end of the 50^s—60^s of the XX century), continuing to study the effectiveness of treatment by representatives who remained in clinical practice, and establishing its clinical predictors (80^s—90^s of the XX century), the appearance of the first data on the effectiveness of therapy for «atypical depression» (1959—1960) and further development of this issue (80^s—90^s of the XX century). The stage of formation and development of the idea of the effectiveness of treatment for resistant depression (late 70^s—90^s of the XX century) is characterized. Separately, the history of studying the effectiveness of application in the USSR and Russia (late 50^s— 90^s of the XX century) is outlined. The current state of the issue of assessing the effectiveness of therapy (the end of the 90^s of the XX century — 2022) is shown.