Since 2000, Clostridium difficile infection has increased substantially in both hospital-acquired and community-acquired diarrhea, not only in North America but also in Europe. There was a steady increase in the incidence and severity of C. difficile infection over the past decade, associated with significantly higher morbidity and mortality. The major risk factors for C. difficile infection appear to be the use of new antimicrobial therapy, long-term hospitalization in old age and emerging hypervirulent strains, such as various ribotypes. Rapid and accurate diagnosis of C. difficile infection is necessary for appropriate treatment as well as reliable epidemiological data. Currently available treatment options are withdrawal of the suspected offending antibiotics and then treating patients with highly effective antibiotics for C. difficile . Multiple recurrence or acute fulminant C. difficile infection could be treated with fecal microbiota transplantation. Promising therapies for treating C. difficile infection should always be equipped with high efficacy and safety in the future.