Most cases of diarrhea-associated hemolytic uremic syndrome (D+HUS) are caused by Shiga toxin-producing bacteria. Shiga toxin-producing Escherichia coli (STEC) O157:H7 has the strongest association worldwide with HUS. A massive outbreak of E. coli O157:H7 infections in Sakai, Osaka, Japan, in 1996 raised public and medical awareness of STEC. However, most cases are sporadic or occur in small clusters. Indeed, more than 100 sporadic or small cluster cases of D+HUS occur every year in Japan. The use of antibiotics in patients with definite or possible enteric STEC infections is controversial; however, there has been no randomized controlled trial to date showing the effectiveness of antibiotics for the prevention of the development of HUS. Thus, most investigators in western countries believe that antibiotics should not be administered to patients with such infections, and the management of HUS remains supportive. There are no specific therapies to ameliorate the course of the disease, and vascular injury leading to HUS is likely to be well under way by the time infected patients seek medical attention for diarrhea. The best way to prevent HUS is to prevent primary infection by Shiga toxin-producing bacteria.