This article is the introduction to a 12-paper supplement on global trends in typhoid fever. The Tackling Typhoid (T2) project was initiated in 2015 to synthesize the existing body of literature on typhoidal salmonellae and study national and regional typhoid fever trends. In addition to a global systematic review, eight case studies were undertaken to examine typhoid and paratyphoid fever trends in endemic countries alongside changes in relevant contextual factors. Incidence variations exist both within and between regions with large subnational differences as well, suggesting that public health changes impacting typhoid and paratyphoid fevers in one setting may not have similar impacts in another. This supplement also brings to light the lack of national typhoid fever surveillance systems, inconsistencies in diagnostics, and the lack of typhoid fever associated morbidity and mortality data in many countries, making it difficult to accurately quantify and track burden of disease. To better understand typhoid fever there is a need for more high-quality data from resource-poor settings. The implementation of typhoid surveillance systems alongside the transition to blood-culture confirmation of cases, where possible, would aid in the improvement of data quality in low-income settings. The following supplement includes the results of our global systematic review, eight-country case study articles, a qualitative article informed by semistructured interviews, and a conclusion article on potential ways forward for typhoid control.