The parasitic protozoa Trypanosoma cruzi and Trypanosoma brucei are responsible for two major tropical infections, Chagas disease and African trypanosomiasis, respectively. These diseases represent a major public health problem in regions of the world least able to deal with the associated economic burden. Advances by ourselves and others have led to the development of a wide range of genetic tools that can be used to address fundamental biological questions associated with these important pathogens. In addition, the output of the trypanosomatid genome projects, together with major advances in imaging technology is providing a research framework where rapid progress can be expected. We are exploiting these new approaches and opportunities to gain greater understanding of the mechanisms of drug action and resistance, and disease pathogenesis. In collaboration with biologists, biochemists and medicinal chemists, we are contributing to the Chagas disease drug discovery pipeline, as well as providing the community with new functional genomic tools. These multidisciplinary approaches, which bring together of both academic and industrial partners, is now widely seen as the way ahead to provide better treatment for these previously ‘Neglected Diseases’.