Clostridium difficile is the leading cause of infectious nosocomial diarrhoea in developed countries, with a measured incidence of approximately five episodes per 10 000 days of hospital stay in Europe. Accurate diagnosis of C. difficile infection (CDI) is a prerequisite for obtaining reliable epidemiological data, but in many European countries diagnosis is probably suboptimal. A significant percentage of CDI cases are missed because clinicians often fail to request tests for C. difficile toxins in cases of unexplained diarrhoea. In addition, some laboratories continue to use tests of low sensitivity or apply them inappropriately. In one study in Spain, failure to request CDI testing in more than two-thirds of patients with unexplained diarrhoea led to significant underdiagnosis of cases. A recent pan-European survey revealed huge discrepancies in the rate of CDI testing across Europe, which suggests that epidemiological reports underestimate the true incidence of CDI in many parts of Europe. This is important because, as this review of the clinical and economic burden of CDI illustrates, infection with C. difficile imposes a significant burden not only on patients, owing to increased morbidity and mortality, but also on healthcare systems and society in general. On the basis of current incidence rates, annual costs for management of CDI amount to approximately $800 million in the USA and €3000 million in Europe. Moreover, estimates suggest that costs associated with recurrent CDI can exceed those of primary CDI. Measures to more effectively prevent CDI and reduce CDI recurrence rates may help to reduce this burden.