Aim: To review pathogenesis of cytokine storm in COVID-19 cases. Background: Human coronaviruses (hCoV) mainly infect upper airways and cause seasonal mild to moderate cold-like respiratory symptoms or severe pneumonia leading to fatal acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Recent clinical investigation reveals that mild COVID-19 patients had high level of IL1B, IFN-γ, CXCL10/IP-10, and CCL2/MCP-1, while patients requiring ICU admission had higher level of GCSF, CXCL10/IP-10, CCL2/MCP-1, and CCL3/MIP-1A, indicating inflammatory cytokine release is critical in COVID-19 progression. IL-1 and IL-6 are responsible for elevation of acute-phase reactants, such as C-reactive protein, serum amyloid A, fibrinogen, hepcidin, and inhibition of albumin synthesis which all together causes a procoagulant environment. In a meta-analysis including nine studies (total 1426 patients), mean IL-6 levels were more than 3 times higher in patients with complicated COVID-19 compared to those with uncomplicated disease, and high IL-6 levels were associated with mortality risk. IL-6 is an important marker of inflammation and can guide the clinicians in recognizing patients with severe COVID-19 early in the disease course. Delay in the interferon release and presence of LPS by secondary bacterial infections increases the severity of cytokine storm. Thus, commencement of early broad-spectrum antibiotic course is advisable. Cytokine storm appears after first week of symptoms when viral load starts decreasing, and this indicates the immunopathogenesis of the ARDS. Conclusion: The aberrant release of multiple cytokines in COVID-19 produces immunopathogenic damage to tissues and organs, even while the immune response tries to overcome the evading mechanisms of virus. Delay in the interferon release and presence of lipopolysaccharide by secondary bacterial infections increase the severity of cytokine storm. IL-6 could be used as a potential marker for severity of the ARDS. However, anti-IL6 antibody Tocilizumab failed to prove effective in clinical trials. Corticosteroid therapy is being given for moderate and severe cases of ARDS, but it needs a very fine balance to outweigh immunosuppressive effects.