Herd immunity is expected to arise when a virus cannot spread readily, because it encounters a population that has a level of immunity that reduces the number of individuals susceptible to infection. On page 288 of this issue, Buss et al. (1) describe the extent of the largely uncontrolled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Manaus, the capital of Amazonas state in Brazil. Their data show the impact on mortality rates of a largely unmitigated outbreak where even with an estimated 76% of the population being infected, herd immunity was not achieved. Manaus provides a cautionary example of unmitigated spread across a population, showing that herd immunity is likely not achieved even at high levels of infection and that it comes with unacceptably high costs.