To use new data to make a revised estimate of the global burden of typhoid fever, an accurate understanding of which is necessary to guide public health decisions for disease control and prevention efforts. Population-based studies using confirmation by blood culture of typhoid fever cases were sought by computer search of the multilingual scientific literature. Where there were no eligible studies, data were extrapolated from neighbouring countries and regions. Age-incidence curves were used to model rates measured among narrow age cohorts to the general population. One-way sensitivity analysis was performed to explore the sensitivity of the estimate to the assumptions. The burden of paratyphoid fever was derived by a proportional method. A total of 22 eligible studies were identified. Regions with high incidence of typhoid fever (>100/100,000 cases/year) include south-central Asia and south-eastAsia. Regions of medium incidence (10-100/100,000 cases/year) include the rest of Asia, Africa, Latin America and the Caribbean, and Oceania, except for Australia and New Zealand. Europe, North America, and the rest of the developed world have low incidence of typhoid fever (<10/100,000 cases/year). We estimate that typhoid fever caused 21,650,974 illnesses and 216,510 deaths during 2000 and that paratyphoid fever caused 5,412,744 illnesses. New data and improved understanding of typhoid fever epidemiology enabled us to refine the global typhoid burden estimate, which remains considerable. More detailed incidence studies in selected countries and regions, particularly Africa, are needed to further improve the estimate.