As a group, vaccines provide a safe and effective way of preventing infectious and allergic illness. Allergic reactions to vaccines and drug products have become important and common features of practice and demand heightened awareness. Serious adverse effects of vaccines are rare but have been reported to various components of different vaccines. Although there are few precise diagnostic tests available, patients usually can be diagnosed accurately after careful attention to the history and physical findings. Better understanding of these reactions can lead to proper vaccine selection and can improve immunization acceptance rates in the community. Prevention, avoidance, use of alternative agents, desensitization, and premedication remain the mainstays of therapy, even as more refined diagnostic and management tools are developed. VAERS data, in addition to the traditional uses (signal detection, large registry of rare vaccine adverse events), can serve as a source of cases for epidemiologic (eg, case-control) studies that evaluate biologic factors that may be related to vaccine-related adverse reactions. Additional studies that are aimed at identifying other causes of immediate hypersensitivity after immunization with live virus vaccines are warranted.