This literature review looks at the epidemiology, clinical manifestations, diagnostics and current medical and surgical management of Clostridium difficile (C. difficile) infection. A literature search of PubMed and Cochrane database regarding C. difficile infection was performed. Information was extracted from 43 published articles from 2000 to the present day which met inclusion criteria. C. difficile is a gram-positive, anaerobic bacillus, which is widely found in the environment, especially in the soil. The occurrence of more resistant strains, which is mainly connected with the wide use of antibiotics, resulted in the rapid spread of the bacteria to different hospital departments. Particularly, elderly patients in surgical wards and intensive care units are at significant risk of developing C. difficile infection, which greatly increases morbidity and mortality. Symptoms of infection with C. difficile vary greatly. At one end of the spectrum, there are asymptomatic carriers, at the other patients with life-threatening toxic megacolon. Metronidazole is considered to be the drug of choice, but recent guidelines recommend Vancomycin. Fulminant colitis and toxic megacolon warrant surgical intervention. The optimal time for surgery is within 48 h of initiating conservative treatment without seeing a response, the development of multiple organ failure or a bowel perforation. A factor that has become increasingly important and relevant is the escalating expense of treatment for patients with C. difficile infection. It is, therefore, highly recommended to consider reviewing all hospital antibiotic policies and clinical guidelines that may contribute to the prevention of the infection.