The clinical progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) to critical illness is associated with an exaggerated immune response, leading to magnified inflammation termed the``cytokine storm ."This response is thought to contribute to the pathogenicity of severe COVID-19 . There is an initial weak interferon response and macrophage activation that results in delayed neutrophil recruitment leading to impeded viral clearance . This causes prolonged immune stimulation and the release of proinflammatory cytokines . Elevated inflammatory markers in COVID-19 (i.e., D-dimer, C-reactive protein, lactate dehydrogenase, ferritin, and interleukin-6) are reminiscent of``cytokine storm"seen in severe hyperinflammatory macrophage disorders . The dysfunctional immune response in COVID-19 also includes lymphopenia, reduced T-cells, reduced natural killer cell maturation, and unmitigated plasmablast proliferation causing aberrant immunoglobulin G levels . The progression to severe disease is accompanied by endotheliopathy, immunothrombosis, and hypercoagulability . Thus, both parts of the immune system-innate and adaptive-play a significant role in the cytokine storm, multiorgan dysfunction, and coagulopathy . This review highlights the importance of understanding the immunological mechanisms of COVID-19 as they inform the clinical presentation and advise potential therapeutic targets.