Babesiosis, caused by piroplasmid protozoans in the genus Babesia, is arguably the most important vector-borne disease of livestock and companion animals and is growing in importance as a zoonosis. Ixodid ticks were identified as vectors more than a hundred years ago, but the particular tick species transmitting some significant pathogens are still unknown. Moreover, it is only recently that the complexity of the pathogen-tick relationship has been revealed as a result of studies enabled by gene expression and RNA interference methodology. In this article, we provide details of demonstrated and incriminated vectors, maps of the current knowledge of vector distribution, a summary of established features of the pathogen life cycle in the vector, and an outline of molecular research on pathogen-tick relationships. The article concludes with a discussion of vector ecology and disease epidemiology in a global-change context and with suggestions for future research.