Over the last 20 years, two sharp disputes concerning vaccine ethics have arisen within the Catholic Church related to (1) whether vaccines utilizing abortion-derived cell lines always must be accepted or may be declined, and (2) the obligation to accept, or the liceity of declining, a novel vaccine recommended or mandated during a pandemic. It appears that the majority of bishops and health care ethicists have supported mandated vaccination in the course of these controversies based on the Church’s longstanding acceptance of the principle and practice of immunization and based on clinical, philosophical, and theological arguments. However, changes in the number and nature of vaccines and information that recently has come to light about established vaccines militates in favor of renewed analyses of the acceptance and arguments of the majority. This chapter advances an approach to making ethical decisions and resolving ethical disputes about vaccines founded on informed consent, key factors in prudential decision-making, and a reconsideration of three principles (charity, stewardship of human life and health, common good) often interpreted as justifying an obligation to accept vaccines. The chapter concludes by considering the status and role of current magisterial teachings on the ethics of vaccine decision-making.