Trypanosomatid parasites infect over 21 million people worldwide, with a range 
of disease phenotypes. Trypanosoma cruzi causes American trypanosomiasis, 
wherein 30-40% of infected individuals develop disease manifestations, most 
commonly cardiomyopathy but also digestive megasyndromes. In the case of 
Trypanosoma brucei, the etiological agent of African trypanosomiasis, disease 
progression can be rapid or slow, with early or late central nervous system 
involvement. Finally, Leishmania species cause leishmaniasis, a disease that 
ranges from self-healing but scarring cutaneous lesions to fatal visceral 
leishmaniasis in which parasites disseminate to the liver, spleen, and bone 
marrow. This review highlights parasite factors involved in disease phenotype in 
all three trypanosomatid diseases, with a particular focus on recent advances 
using large-scale 'omics' techniques.