Most cases of human babesiosis are successfully treated with atovaquone plus azithromycin or clindamycin plus quinine. A major research topic is the management of immunocompromised hosts, especially those experiencing severe or relapsing babesiosis. Two immediate goals are, (i) to develop new antimicrobial agents that target Babesia spp. through novel mechanisms and can overcome resistance to currently recommended antimicrobial agents and, (ii) to gain a better understanding of the efficacy of red blood cell exchange transfusion and indications for its use.