Public trust in immunization programs can be damaged more quickly than it can be rebuilt. Because anxiety regarding vaccines can come from a complex range of cultural, political, religious, and social forces, addressing concerns can be complicated, difficult, and time consuming. While evidence-based science can play a role in building confidence in vaccines and immunization programs, addressing specific situations where vaccine hesitancy is flourishing requires a range of expertise. This chapter discusses both effective and ineffective responses to specific cases of vaccine hesitancy and refusal and offers suggestions for how to craft effective responses when future crises arise.