It is hoped that worldwide vaccination will help to end the COVID-19 pandemic, but vaccination combined with relaxed social distancing is likely to drive vaccine resistance. Can policymakers prevent the emergence of vaccine-resistant variants of SARS-CoV-2? To address this, Lobinska et al. used mathematical modelling to assess the evolution of vaccine-resistant strains of SARS-CoV-2 in the presence of dynamic social distancing. They used real-world infection and vaccination data from six countries to inform their model and conclude that if the rate of vaccination is slow, resistance is likely to emerge even if social distancing is maintained. However, under fast vaccination, the emergence of variants can be prevented if social distancing is maintained during vaccination. They caution that social distancing measures should be maintained until the daily number of infections is substantially decreased. Allowing a large number of daily infections can only be counterbalanced by very high vaccination rates — otherwise vaccine-resistant variants of SARS-CoV-2 are likely to emerge.