Since its launch in 1988, the Global Polio Eradication Initiative has grown into one of the largest international health efforts in history, operating in every country and area in the world. The burden of polio disease has been reduced by over 99%, and the number of countries with indigenous virus has fallen from more than 125 to just four. As importantly, a strong surveillance and laboratory infrastructure has been established for vaccine-preventable diseases (including measles, tetanus, yellow fever, rubella and Japanese encephalitis), and a massive investment has been made in the physical infrastructure and human resources needed to deliver routine immunizations and other health services in developing countries. Between 2000 and 2003, new challenges to polio eradication emerged, threatening the interruption of the transmission of wild poliovirus globally and the eventual elimination of any residual polio disease as the result of the continued use of oral polio vaccines. By the end of 2005, a range of solutions had been developed to address these late challenges, including two new monovalent oral polio vaccines, new and robust international standards for the response to polio outbreaks, and renewed political commitment across the countries that remain infected. As importantly, a comprehensive strategy had been established for managing the long-term risks of paralytic polio, centred, ironically, on the eventual elimination from routine immunizations of the vaccine that is still central to the success of the global eradication effort.