Diarrhea caused by infection with rotavirus annually results in an estimated 611,000 deaths among infants and young children <5 years of age worldwide, and these deaths primarily occur in developing countries. Infection with human immunodeficiency virus (HIV) is also common among young children in many developing countries, particularly in sub-Saharan Africa and Asia. The need for a vaccine to reduce the number of deaths caused by rotavirus infection among children in developing countries is substantial, but current rotavirus vaccines comprise live attenuated oral viruses, the behaviors of which are unknown in HIV-infected children. Therefore, we reviewed available data on natural rotavirus infection in HIV-infected children and examined unpublished data on a small group of HIV-infected infants in South Africa who were given a live rotavirus vaccine. Together, these data suggest that vaccination programs against rotavirus infection could include HIV-infected populations. However, studies addressing the safety, reactogenicity, and immunogenicity of rotavirus vaccines in an HIV-infected population are urgently needed.