Rotavirus remains the most common cause of severe childhood diarrhea worldwide and of diarrheal mortality in poor countries. In 2003, the GAVI Alliance launched the Rotavirus Vaccine Program and the Accelerated Development and Introduction Plan to close the gap of access to rotavirus vaccines in industrialized and developing countries by generating data on rotavirus disease burden, projected impact, and cost-effectiveness of vaccination and by conducting clinical trials of existing vaccines in impoverished settings. By the end of 2008, rotavirus vaccines were licensed in >100 countries, although only 17 countries have introduced routine rotavirus vaccination. Increased uptake of the vaccine by countries with the highest childhood mortality will depend in part on a solid evidence base of estimated burden and cost of rotavirus illness. Since 2001, regional surveillance networks worldwide have generated burden and strain data from 196 sites in 59 countries. Among children aged <5 years who are hospitalized for severe diarrhea in different regions of the world, a regional median of 39% (range by country, 20%-73%) test positive for rotavirus. Rotavirus vaccines are a cost-effective intervention and may be cost saving with a GAVI Alliance subsidy from the health care perspective. Punctual vaccination and high coverage of populations at highest risk of mortality will maximize the impact of vaccination. Surveillance platforms will allow measurement of the rapid impact of rotavirus vaccine introduction on the heavy burden of rotavirus on child health worldwide.