Immunization of livestock against the erythroparasitic pathogens Anaplasma marginale, Babesia bigemina, and Babesia bovis with safe and effective killed vaccines is not yet feasible on a practical basis. However, the immune protection afforded by recovery from natural infection and premunition indicates that microbial epitopes capable of inducing immunity exist and that the bovine immune system can be primed appropriately. Induction of protection by immunization with killed parasite fractions, enriched for polypeptides with surface exposed epitopes, supports a focus on surface epitopes, including apical complex organellar epitopes in Babesia, for vaccine development. Cloning, sequencing, and expression of genes encoding these key surface polypeptides has allowed examination of polypeptide function and detailed analysis of epitope conservation in light of genetic polymorphism. In this paper, the characterization of these polypeptides at the epitope level and their roles in inducing protective immunity are reviewed. Definition of these epitopes, in combination with improved understanding of immune mechanisms, provides the basis for development of effective recombinant vaccines against anaplasmosis and babesiosis.