Public health professionals believed the pandemic would end with public embrace and even celebration of vaccination as had occurred in past communicable disease outbreaks such as measles and polio but exactly the opposite occurred. The introduction of COVID-19 vaccination amplified a pre-existing anti-vaccine movement in the United States and worldwide while generating new public fears, hesitations, and concerns about vaccination. Social media and the internet spread dis- and misinformation saturated in fear that clouded scientific data and diminished expert voices. Vaccine hesitancy is not a symptom of public ignorance but of mistrust—a lesson that must be studied and considered moving forward in public health efforts.