question: Some drugs with immunomodulatory and anti-inflammatory activity are identified as adjunctive therapy in the coronavirus disease 2019 (COVID-19) infections and researchers believe that such pathophysiologic pathway treatment approach is rational and important for future development of new therapeutic agents in managing this pandemic. This review will discuss various cytokines which go berserk and cause serious life-threatening complications in COVID-19 infections. Additionally, different therapeutic modalities in managing 'cytokine storm,' with a special note on melatonin is discussed. The foundation laid by scientists on this wonder molecule may pave the path toward development of drug with satisfactory results either used alone or as an adjunct to other drugs. However, calming the angered cytokine profile seems pivotal during management of the devastating storm. © 2021 Wolters Kluwer Medknow Publications. All rights reserved.