OBJECTIVE Rotavirus infection is the leading cause of severe dehydrating gastroenteritis, responsible for an estimated 440,000 deaths per year in children less than 5 years of age worldwide. There was great optimism when the first rotavirus vaccine was licensed in the United States in July 1998 (rhesus rotavirus tetravalent, RRV-TV, Rotashield, Wyeth Laboratories, Marietta, PA). However, 9 months after the vaccine become available, the rotavirus immunization program was suspended due to reports of an association between the vaccine and intussusception. The estimation of risk of intussusception with Rotashield immunization has been the subject of debate and is discussed in this review. RESULTS The risk of intussusception following Rotashield immunization is estimated to be between 1 in 10,000 to 1 in 32,000 vaccinees. The risk is highest during the 3 to 14 days following receipt of the first dose of vaccine. Infants older than 3 months at the time of the first dose of vaccine are at increased risk of intussusception. CONCLUSIONS The association between Rotashield and the development of intussusception has presented a major challenge to the development of rotavirus vaccines. Intussusception risk is greatest in the first 3 to 14 days following the receipt of the first dose of Rotashield in infants older than 3 months of age. Although there continues to be debate surrounding the exact quantitation of risk of intussusception, it is accepted as a rare adverse event. The development of alternate rotavirus vaccines and emerging manufacturers in developing countries has renewed optimism for the reduction of the global burden of rotavirus disease.