Human genetics can inform the biology and epidemiology of coronavirus disease 2019 (COVID-19) by pinpointing causal mechanisms that explain why some individuals become more severely affected by the disease upon infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Large-scale genetic association studies, encompassing both rare and common genetic variants, have used different study designs and multiple disease phenotype definitions to identify several genomic regions associated with COVID-19. Along with a multitude of follow-up studies, these findings have increased our understanding of disease aetiology and provided routes for management of COVID-19. Important emergent opportunities include the clinical translatability of genetic risk prediction, the repurposing of existing drugs, exploration of variable host effects of different viral strains, study of inter-individual variability in vaccination response and understanding the long-term consequences of SARS-CoV-2 infection. Beyond the current pandemic, these transferrable opportunities are likely to affect the study of many infectious diseases.