Babesia bovis and Babesia bigemina are protozoan parasites of the Apicomplexa phylum that cause bovine babesiosis, a cattle disease transmitted by ticks of the Rhipicephalus genera. It is a disease of the tropical and subtropical regions, therefore in Mexico, it is present in 51.5% of the national territory. The severe negative impact of cattle ticks and bovine babesiosis on the livestock industry in Mexico and the world persists due to the absence of safe and effective commercial vaccines. Vaccines based on genomics and biotechnological tools promise to be a solution to this problem. With the complete genome sequence of Babesia bovis and Babesia bigemina, genomic studies of these pathogens are now possible and valuable information is available on the essential characteristics of their composition and their comparison with the other Apicomplexa protozoa of importance in human and animal health, as well as the identification of new genes with vaccination or therapeutic potential. In this chapter, we review the latest knowledge in the cellular and molecular mechanisms that trigger a protective, immune response and the identification of the molecular targets for vaccine development, all of which are a key priority to develop control measures against these pathogens.