The rapid development of safe and efficacious vaccines against SARS-CoV-2 has offered hope that the global COVID-19 pandemic may soon be under control. However, vaccinations remain incomplete in many developed nations, and lag further still in the developing world. In a new Focus, Jonathan Sprent and Cecile King posit that vaccine hesitancy, motivated in part by fear of side effects documented in scientific journals and the popular media, could hold back the global population from reaching herd immunity. Seeking to reassure those with reservations, Sprent and King suggest that "it is highly likely - albeit not proven - that the side effects of COVID-19 vaccines are simply a by-product of a short burst of [type I interferon] generation concomitant with induction of an effective immune response." Thus, they contend that "the prospect of fatigue and headache after vaccination for COVID-19 should be viewed positively: as a necessary prelude to an effective immune response."