Human infections with Babesia species, in particular Babesia microti, are tick-borne illnesses that are being recognised with increased frequency. Coinfection with ehrlichiosis and Lyme disease is also being recognised as an important feature of these tick-borne illnesses. Despite the superficial resemblance of Babesia to malaria, these piroplasms do not respond to chloroquine or other similar drugs. However, the treatment of babesiosis using a clindamycin-quinine combination has been successful. Data in animal models and case-reports in humans have suggested that an atovaquone-azithromycin combination is also effective. This was confirmed in a recent prospective, open, randomised trial of clindamycin-quinine versus azithromycin-atovaquone. This paper reviews the literature on the treatment of human babesiosis and the animal models of these human pathogens.