Background:Clostridium difficile has become recognized as a cause of nosocomial infection which may progress to a fulminant disease. Methods: Literature review using electronic literature research back to 1966 utilizing Medline and Current Contents. All publications on antibiotic-associated diarrhea, antibiotic-associated colitis, and pseudomembranous colitis as well as C. difficile infection were included. We addressed established and potential risk factors for C. difficile disease such as an impaired immune system and cost benefits of different diagnostic tests. An algorithm is outlined for diagnosis and both medical and surgical management of mild, moderate and severe C. difficile disease. Results: Diagnosis of C. difficile infection should be suspected in patients with diarrhea, who have received antibiotics within 2 months or whose symptoms started after hospitalization. A stool specimen should be tested for the presence of leukocytes and C. difficile toxins. If this is negative and symptoms persist, stool should be tested with ‘rapid’ enzyme immunoabsorbent and stool cytotoxin assays, which are the most cost-effective tests. Endoscopy and other imaging studies are reserved for severe and rapidly progressive courses. Oral metronidazole or vancomycin are the antibiotics of choice. Surgery is rarely required for selected patients refractory to medical treatment. The threshold for surgery in severe cases with risk factors including an impaired immune system should be low. Conclusion:C. difficile infection has been recognized with increased frequency as a nosocomial infection. Early diagnosis with immunoassays of the stool and prompt medical therapy have a high cure rate. Metronidazole has supplanted oral vancomycin as the drug of first choice for treating C. difficile infections.