A cluster of unexplained pneumonia in late-2019 was the preface to a rapid-spreading global health crisis sparked by emergence of a novel coronavirus (SARS-CoV-2). Since its emergence, the highly contagious SARS-CoV-2 illness Coronavirus disease 2019 (COVID-19) has affected millions of people worldwide and triggered a rapid scientific movement to map case statistics, understand disease pathophysiology and find efficacious treatments for this insidious disease. Clinical case studies consistently report that being male is a major risk factor for COVID-19 morbidity and mortality. In one study covering 1099 adults admitted to 552 mainland China hospitals, 70% of patients requiring ventilation support in intensive care were biologically male (Guan et al, 2020, N Eng J Med). This was corroborated in reports of COVID-19 mortality across 38 countries, where the fatality rate of men was 1.7-fold higher than women (Scully et al, 2020, Nat Rev Immunol). Albeit, in paediatric studies this gender gap was not evident; prepubescent females and males were equally impacted by mild/moderate COVID-19 (Wu et al, 2020, JAMA Netw Open). These observations of distinct sex-specific disparities in the course of COVID-19 disease have triggered rigorous inquiry into the role of sex hormones in driving SARS-CoV-2 virus susceptibility and illness severity. Evolving evidence suggests male sex hormones, androgens, regulate the SARS-CoV-2 receptor, Angiotensin-Converting Enzyme 2 (ACE2), and co-receptor, Type II Transmembrane Serine Protease (TMPRSS2), which facilitate SARS-CoV-2 entry and infection of host cells. Furthermore, the host’s sex hormone milieu influences the immune response mounted in response to SARS-CoV-2 respiratory infection and the release inflammatory cytokines including interleukin-6 (IL-6) which is markedly elevated in severe COVID-19 infection and exhibits excessive secretion in males. In conclusion, the emerging intersection between androgens and COVID-19 may pave the way for hormone rationalised therapies to effectively lower disease severity across patients affected by severe COVID-19 illness.