What will the SARS-CoV-2 outbreak look like ten years from now as it passes from pandemic to endemic, maintained at a constant baseline level in populations without being fueled by outside infections? Data from four endemic human coronaviruses, which circulate globally and cause only mild symptoms, may hold some answers, say Jennie Lavine and colleagues. Their analysis of the immunological and epidemiological data for these viruses helped them develop a model to predict the trajectory of SARS-CoV-2 as it becomes endemic. Most importantly, the authors say, their model incorporates distinct components of immunological protection--susceptibility to reinfection, weakening of the disease after reinfection, and transmissibility of the virus after reinfection--that each wane differently. Lavine et al. suggest that endemic SARS-CoV-2 may become a disease of early childhood, where the first infection occurs between 3 and 5 years old, and the disease itself would be mild. Older individuals could still become infected, but their childhood infections would provide immune protection against severe disease. How fast this shift comes depends on how fast the virus spreads and what kind of immune response the SARS-CoV-2 vaccines induce. If the vaccines induce short-lived protection against becoming reinfected but reduce the severity of the disease, as is the case with other endemic coronaviruses, SARS-CoV-2 may become endemic more quickly, the model suggests. The authors also note that if primary infections of children are mild when the virus becomes endemic, widespread vaccination may not be necessary. But if primary infections become severe in children, as in the case of more deadly but contained coronaviruses such as MERS, childhood vaccinations should be continued.