Vaccines have features that require special consideration when assessing their cost-effectiveness. These features are related to herd immunity, quality-of-life losses in young children, parental care and work loss, time preference, uncertainty, eradication, macroeconomics, and tiered pricing. Advisory committees on public funding for vaccines, or for pharmaceuticals in general, should be knowledgable about these special features. We discuss key issues and difficulties in decision making for vaccines against rotavirus, human papillomavirus, varicella-zoster virus, influenza virus, and Streptococcus pneumoniae. We argue that guidelines for economic evaluation should be reconsidered generally to recommend (1) modelling options for the assessment of interventions against infectious diseases; (2) a wider perspective to account for impacts on third parties, if relevant; (3) a wider scope of costs than health-care system costs alone, if appropriate; and (4) alternative discounting techniques to explore social time preference over long periods.