The US response to coronavirus disease 2019 (COVID-19) has been plagued with politics driving public health and messaging. As a result, COVID-19 vaccine rollout is occurring in an environment ill equipped to achieve broad acceptance of the vaccine. Addressing public concerns unlocks the potential for high vaccine coverage; this is best achieved when science and values, not politics, inform public health. A multifaceted and thorough engagement and communication plan that is responsive to the concerns and values of different groups must be swiftly yet carefully implemented in a coordinated manner by federal, state, and local governments. Effective communication will require rapid and rigorous science to promptly differentiate between adverse events following immunization that are causally related versus simply coincidental. Health care providers, in particular, will need support to process the otherwise potentially overwhelming amount of relevant information and effectively integrate it into discussions with their patients to support their decision making. An equitable COVID-19 immunization program could substantively reduce the disproportionate risks associated with this pandemic.