Anaphylaxis is a treatable condition with no permanent effects. Nevertheless, news of these reactions has raised fear about the risks of a new vaccine in a community. These cases of anaphylaxis raise more questions than they answer; however, such safety signals are almost inevitable as we embark on vaccination of millions of people, and they highlight the need for a robust and proactive “safety roadmap” to define causal mechanisms, identify populations at risk for such reactions, and implement strategies that will facilitate management and prevention (Figure 1).6