Monoclonal antibody (mAb) therapies have shown some use in patients with mild to moderate COVID-19, but have limited efficacy in preventing complications or death in patients with severe COVID-19. Reporting in Nature, Ravetch, Bournazos and colleagues now demonstrate that optimizing mAbs for the engagement of activating Fcγ receptors (FcγRs) significantly improves their ability to confer full protection in SARS-CoV-2 challenge models. Moreover, these mAbs are also highly potent at reducing mortality post-infection in animal models of severe COVID-19. These findings illustrate the importance of FcγR-mediated pathways in antibody-mediated antiviral immunity and have important implications for the development of more effective mAb therapeutics.