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Babesiosis is a zoonosis, a disease communicable from animals to man. The rodent parasite, Babesia microti and the bovine pathogen, Babesia divergens are responsible for most of the human infections that have been reported to date, globally. From a blood safety perspective, transfusion-transmitted infections involving Babesia spp. have become increasingly problematic in the USA. Therefore, the study of this blood-borne parasite should be considered as a priority for transfusion medicine. Our purpose is to understand the invasion process of B. divergens into the human RBC, with the ultimate aim of exploiting parasite molecules found to play key roles in invasion as diagnostic and blood screening tools. The in-vitro system that we use for studying invasion of the human red cell by B. divergens permits direct exploration of the events associated with parasite invasion of the human RBC, using viable merozoites of B. divergens. Molecules on the surface of the parasite and those secreted by apical organelles function at the host/parasite interface, and we need to identify them and determine their interactions and function, if we are to define the steps in the invasion mechanism and identify new therapeutic targets. We have identified multiple parasite molecules that bind the human RBC, and we will present results on their identification, characterization and potential RBC receptors. We anticipate the study of molecular mechanisms involved in the entry of Babesia merozoites into the RBC will result in reagents for diagnosis, epidemiology and treatment and prevention of human babesiosis and assist in developing products to screen blood products.