The outbreak of Coronavirus disease 2019 (COVID-19) is the current world health concern, presenting a public health dilemma with ascending morbidity and mortality rates exceeding any previous viral spread, without a standard effective treatment yet. SARS-CoV-2 infection is distinguished with multiple epidemiological and pathological features, one of them being the elevated levels of cytokine release, which in turn trigger an aberrant uncontrolled response known as “cytokine storm”. This phenomenon contributes to severe acute respiratory distress syndrome (ARDS), leading to pneumonia and respiratory failure, which is considered a major contributor to COVID-19-associated fatality rates. Taking into account that the vast majority of the COVID-19 cases are aggravated by the respiratory and multiorgan failure triggered by the sustained release of cytokines, implementing therapeutics that alleviate or diminish the upregulated inflammatory response would provide a therapeutic advantage to COVID-19 patients. Indeed, dexamethasone, a widely available and inexpensive corticosteroid with anti-inflammatory effects, has shown a great promise in reducing mortality rates in COVID-19 patients. In this review, we have critically compared the clinical impact of several potential therapeutic agents that could block or interfere with the cytokine storm, such as IL-1 inhibitors, IL-6 inhibitors, mast cell-targeted agents, and corticosteroids. This work focused on highlighting and contrasting the current success and limitations toward the involvement of these agents in future treatment protocols.Copyright © 2020. Published by Elsevier Inc.