The epidemiology of Clostridium difficile infection (CDI) has changed over the past decade. There has been a dramatic worldwide increase in its incidence, and new CDI populations are emerging, such as those with community-acquired infection and no previous exposure to antibiotics, children, pregnant women and patients with IBD. Diagnosis of CDI requires identification of C. difficile toxin A or B in diarrheal stool. The accuracy of current diagnostic tests remains inadequate and the optimal diagnostic testing algorithm has not been defined. The first-line agents for CDI treatment are metronidazole and vancomycin, with the latter being the preferred agent in patients with severe disease as it has significantly superior efficacy. The incidence of metronidazole treatment failures has increased, emphasizing the need to find alternative treatment options. Disease recurrence continues to occur in 20-40% of patients and its treatment remains challenging. In patients with CDI who develop fulminant colitis, early surgical consultation is essential. Intravenous immunoglobulin and tigecycline have been used in patients with severe refractory disease but delaying surgery may be associated with worse outcomes. Infection control measures are key to prevent horizontal transmission of infection. Ongoing research into effective treatment protocols and prevention is essential.