This review presents the microbiology, management and prevention of pseudomembranous colitis (PMC) in children. PMC is commonly associated with prior antibiotic exposure and hospitalization. It is caused almost exclusively by toxins produced by Clostridium difficile. The clinical spectrum of this disease may range from a mild, non-specific diarrhea to severe colitis with toxic megacolon, perforation, and death. PMC may affect all age groups, although a lower incidence has been noted in children. Ampicillin, amoxicillin, the second- and third-generation cephalosporins and clindamycin are the drugs most frequently associated with development of PMC, although nearly all antimicrobials have been implicated as causes of diarrhea and colitis. Discontinuation of antibiotics and supportive therapy usually lead to resolution of this disorder. Administration of oral vancomycin or other therapeutic regimens may be needed.