C. difficile is the most common infectious cause of healthcare-associated diarrhea but now is increasingly recognized as a cause of diarrhea in outpatients and persons without apparent health care contacts. Emergence and spread of new epidemic clones of C. difficile 027 (PCR-ribotype) and 078/126 (toxinotype) with increase toxin production, an aditional binary toxin and high level resistance to fluoroquinolones and increasing incidence of more rapidly progressive severe disease, require prompt clinical recognition and new tools to predict severity and to prevent recurrences. Although antibiotics are effective at inhibiting C. difficile and treating symptoms, these drugs could not reestablish normal bowel flora and the rate of recurrences is 25%. During the past years we assisted to an impressive search for new and more effective therapy that shoud be save, with low potential for the development of resistance, with low levels of systemic absorbtion and high levels of active drug in the colon and should be associated with a low rate of recurrence after treatment. By consequence, different approaches to the management of recurrent infections have been studied such as new antibiotics (fidaxomicin), human monoclonal antibodies against C. difficile toxins A and B, intravenous human immunoglobulin, active immunization, and probiotic therapy.