INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a dysregulated hyperinflammatory response . AREAS COVERED: The authors review evidence on IL-6 and IL-6 blockade in coronavirus disease 2019 (COVID-19) and discuss the pathophysiological and prognostic roles of this cytokine and the clinical impact of pharmacological blockade of IL-6 blockade . Material includes original articles and reviews published from March 2020 to March 2021 and searched on PubMed, medRxiv, and bioRxiv . EXPERT OPINION: IL-6 is one the most prominent inflammatory cytokines . Increased levels were recorded in COVID-19 patients, especially those with severe-to-critical disease . Evidence is accumulating on the relevance of IL-6 as a prognostic marker in COVID-19, including need for mechanical ventilation and death . Since IL-6 is a druggable target for several inflammatory diseases, blockers of the IL-6 signaling pathway were repurposed to block the abnormal SARS-CoV-2-induced cytokine release . Data are limited to few randomized controlled trials that reported encouraging, though not conclusive, results, indicating the usefulness of IL-6 blockade early in the course of disease in patients with hyperinflammation and no or limited organ damage . Further research is warranted to explore the role of IL-6 in different COVID-19 phenotypes and identify subgroups of patients who may mostly benefit from IL-6 pathway inhibition.