The recent mumps epidemic in the central United States has generated a large amount of public concern. A total of 2597 mumps cases have been reported in the United States in 11 states since January 1, 2006, representing a marked resurgence of mumps in a single year. The majority of these recent cases have occurred in college students age 18 to 25 years. Most were vaccinated with 2 doses of measles, mumps, and rubella-containing vaccines. Such outbreaks provide an opportunity for clinicians to review the clinical presentation, diagnosis, and morbidity of vaccine-preventable infections and also to review immunologic mechanisms and practice guidelines that might contribute to poor vaccine responses. A review of mumps is provided with discussion of potential mechanisms for vaccine failure.