Technical Abstract: Tick-borne protozoa impose a significant health burden on humans and animals throughout the world. The virulence of tick-borne protozoa, and the geographic distribution of their tick vectors and vertebrate hosts remain in flux as they adapt to changing environmental and climatic conditions. Babesiosis and theileriosis are among the most prevalent tick-borne diseases of cattle. They inflict millions of dollars in losses to the livestock industry and cause poverty among pastoralists in developing societies. In the post-genomic era, scientists are starting to fill some of the gaps in our knowledge of the biology of Babesia bovis and Theileria parva. Interdisciplinary studies that explore tick-protozoa-host interactions will provide an important foundation to develop enhanced prevention and therapeutic strategies for bovine babesiosis and theileriosis. Human babesiosis was discovered more recently but the number and range of cases have dramatically increased over the last decade. As both tick-borne and transfusion transmitted babesiosis continue to emerge, epidemiologic studies are needed to better assess the location of current and future endemic areas, the incidence of disease, and the genetic makeup of the etiologic agents involved. Ongoing taxonomic investigations and molecular diagnostics research are expected to reveal great diversity within the genus Babesia. Studies also are needed to characterize the pathogenesis of human babesiosis, particularly in the context of aging hosts and co-infection by other tick-borne pathogens. Diagnostic tests should be improved and adapted to screen the blood supply to prevent transfusion-transmitted babesiosis. New antimicrobial therapeutic combinations are needed for the treatment of severe babesiosis in immunocompromised patients. An integrated research approach will help mitigate the impact of tick-borne protozoal diseases and improve the health of humans, domestic animals, and wildlife.