Clostridium difficile infection (CDI) has become an important area in our daily clinical practice. C. difficile is known to cause a broad spectrum of conditions ranging from asymptomatic carriage, through mild or moderately severe disease with watery diarrhoea, to the life-threatening pseudomembranous colitis (PMC), with toxic megacolon and ileus. Peoples who have been treated with broad-spectrum antibiotics, patients with serious underlying co-morbidities and the elderly are at greatest risk. Over 80% of CDIs reported are in people aged over 65. Due to the alarming increase in its frequency, appearance of more virulent strains and occasional need for life-saving surgical intervention, a more coherent multidisciplinary approach is needed. Combination of rapid turn round time and accurate diagnosis will result in a better management of CDI and a timely implementation of infection control measure. Discontinuation of causative agents such as antibiotic treatment is often curative. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice. Relapses of CDI have been reported in about 20-25% of cases, this may increase to 45-60% after the first recurrence. Patients should be treated as soon as possible when the diagnosis of Clostridium difficile colitis is made to avoid sepsis or bowel perforation. Colectomy may improve the outcome of the patient with systemic or complicated Clostridium difficile colitis. This article reviews the changing epidemiological picture, microbiology, histopathology and both medical and surgical managements.