Since 1957, there have been 22 reported cases of human babesiosis in splenectomized persons, representing about one third of all clinical human babesiosis. Splenectomy had been performed one month to 36 years (mean 8.7 years, median 6.0 years) earlier for a variety of reasons. Four of the seven European cases were from Babesia divergens whereas 12 of the 15 United States cases were from B. microti. Most of the 22 patients had moderate to severe clinical disease including hemolytic anemia, yet all but six recovered. Three patients had transfusion-acquired babesiosis. Treatments employed included the use of chloroquine, quinine, pyrimethamine, pentamidine, clindamycin, dialysis, and exchange transfusion. Splenectomized and/or otherwise immunocompromised hosts should be advised to avoid visiting endemic areas for babesiosis such as Nantucket Island or Martha's Vineyard in Massachusetts and Shelter Island and other parts of Long Island, New York. Babesiosis must be considered as one of the not uncommon organisms responsible for the postsplenectomy sepsis syndrome and one for which there is no current prophylaxis.