"The urgent need for COVID-19 vaccines must be balanced with the imperative of ensuring safety and public confidence in vaccines by following the established clinical safety testing protocols throughout vaccine development, including both pre- and post-deployment," write David M. Knipe and colleagues in this Perspective. The authors highlight how historical experience with vaccine development has paved the way for a well-developed path for preclinical and clinical testing to ensure vaccine safety and efficacy. COVID19 vaccines will be safe if regulatory agencies maintain their well-documented safety testing protocols, as informed by history, they say. As part of this process, all batches of vaccines must be tested for safety. Also, it is critical for developers to understand a vaccine's mechanism of action and immune correlates of protection; understanding these can ensure that vaccines induce the optimal immune response for protection while avoiding nonproductive or counterproductive immune responses. Another lesson learned from historical vaccine development, Knipe and colleagues write, is that if serious adverse events are detected in a clinical trial, then additional clinical testing is indicated. Current regulatory practices require monitoring of rare adverse events pre- and post-licensure of a vaccine, with detection of serious adverse events triggering a pause to trial or use. Indeed, Knipe et al. note, such safety pauses have occurred in current COVID-19 vaccine trials, underscoring the value of extensive regulatory safety protocols, which should not be rushed or undermined. "There is an urgent need for COVID-19 vaccines and exciting progress to that end," write Knipe et al., "but there remains a critical public health obligation to conduct rigorous evaluation to ensure safety as well as efficacy."