Two reports in The New England Journal of Medicine in January 2010 arrived with the news that rotavirus (Figure) vaccines have the potential to substantially decrease severe illness and the risk of death from diarrhea in infants and children. As the leading cause of severe diarrhea in both developed and developing countries, infection with rotavirus results in over half a million deaths each year. In a placebo-controlled, multicenter trial to evaluate efficacy to prevent severe rotavirus gastroenteritis, 3,166 infants in South Africa and 1,773 in Malawi were randomly assigned to receive 2 doses of live, oral retrovirus vaccine, in addition to 1 dose of placebo or 3 doses of vaccine—the pooled vaccine group. A third group received 3 doses of placebo at 6, 10, and 14 weeks of age. During active surveillance in the first year of life, severe rotavirus gastroenteritis occurred in 4.9% of infants in the placebo group versus 1.9% in the pooled vaccine group. The authors, led by Shabir A. Madhi, MD, of the University of Witwatersrand in Johannesburg and. Nigel A. Cunliffe, MB, ChB, PhD of the University of Liverpool in the United Kingdom, found vaccine efficacy lower in Malawi than in South Africa (49.9% vs 76.9%; pooled efficacy, 61.2%). However, they note that in Malawi the vaccine prevented more episodes of severe rotavirus gastroenteritis than in South Africa or in other regions where it had been evaluated. Efficacy against severe gastroenteritis from all causes was 30.2%. A postmarketing study in Mexico looked at the effect of vaccination on deaths from diarrhea in children <5 years of age in 2008 and 2009. The study was conducted after a phased introduction of a monovalent rotavirus vaccine from February 2006 through May 2007. “By December 2007, an estimated 74% of children who were 11 months of age or younger had received 1 dose of rotavirus vaccine,” write coauthors from the National Center for Child and Adolescent Health in Mexico City and from the US Centers for Disease Control and Prevention in Atlanta, Georgia. By 2008, the researchers led by the Centers for Disease Control and Prevention's Manesh Patel, MD, of the National Center for Immunization and Respiratory Diseases, found that diarrhea related mortality among 5 year olds fell from the annual median of 1,793 deaths during 2003–2006 to 1,118, a drop of 675. Moreover, “diarrhea-related mortality fell from an annual median of 18.1 per 100,000 children at baseline to 11.8 per 100,000 children in 2008,” a rate reduction of 35%. Among infants ≤11 months of age, there was a 41% decline in diarrhea-related mortality and a 29% decline for children 12–23 months of age, compared with baseline. These significant declines persisted through 2 full rotavirus seasons, 2008–2009, the authors state. In his accompanying editorial, Mathuram Santosham, MD, MPH, from The Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, writes: “The data support the use of rotavirus vaccines in the poorest countries of the world, a finding that is consistent with previous reports.” He points to “considerable challenges” to implementing their use in these countries, among these storage and shipment requirements “to avert cold-chain breaks of rotavirus vaccines,” that are far greater than those of typical childhood vaccines. In addition to issues surrounding vaccine costs that require continual donor community support, is the narrow vaccine administration window that could have the greatest negative impact in countries with the lowest vaccine coverage and lowest rate on on-time immunization. Still, Patel concludes: “We now have another powerful weapon to add to armamentarium to combat deaths from diarrhea—rotavirus vaccines.” See N Engl J Med, 2010;362:289–298.