The tick-transmitted Babesia and Theileria spp. parasites are detrimental for animal health and cattle production in vast tropical and subtropical areas of the world. Additionally, human babesiosis increasingly raises public health concern. Most of the research on these piroplasmids has been focused on mammal-infecting stages, while the interaction with their tick vectors has been widely neglected. For millions of years, piroplasmids have been able to effectively exploit the tick milieu to carry out critical parts of their life cycle; including self propagation, sexual reproduction and recombination, development of infective forms capable of returning to their mammalian hosts through tick saliva, and in many cases, perpetuation into the next tick generation. Although piroplasmid colonization can seriously damage tick tissues and organs, innate immune mechanisms seem to be able to control these effects. This paper reviews the molecular interactions between ticks and piroplasmids from different perspectives. A deeper understanding of this interface might lead to the design of new control strategies.