This review analyzes existing approaches to the treatment of COVID-19 patients with antimalarial drugs from the standpoint of rational pharmacotherapy. Particular attention is paid to drug interactions and side effects of co-administration of chloroquine/hydroxychloroquine and azithromycin, considering the problem of cardiotoxicity and the high likelihood of cardiovascular disease in middle-aged and elderly people with COVID-19. The article discusses the prospects of using another representative from the group of antimalarial drugs - mefloquine in the treatment of COVID-19. Special attention is paid to the "proarrhythmogenic" side effects of azithromycin therapy, as well as to the problem of resistance of microorganisms to macrolides during antibiotic therapy of pneumonia, in particular to azithromycin. In conclusion, the article discusses the possibilities of alternative methods in the treatment of this disease. © 2020 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.