Clostridium difficile-associated diarrhea usually occurs as a complication of antibiotic treatment. Recent data shows an increase in incidence rate of CDAD and higher rates of morbidity, colectomy and death. The management of CDAD involves discontinuing the inciting antibiotic agent and treatment with metronidazole or vancomycin. The reduced response rates and higher recurrence rates with metronidazole treatment reported in recent studies raise the question of the effectiveness of metronidazole therapy. After each recurrence, the risks for further relapses grow even bigger (after two recurrences, the risk being greater than 50%) and the management of recurrent CDAD becomes a challenge. Even after a careful review of available data on various drugs and having the experience of managing many cases of CDAD, one might find difficult to present with a successful "recipe" for treating severe CDAD. Every case is different and different management plans can lead to full recovery. First episode are metronidazole. If there is no improvement in three days or white blood cell count is more than 12,000 or creatinine level is high, metronidazole should be discontinued and vancomycin should be started. The latest trend of CDAD with more severe cases and increasing morbidity and mortality may be an incentive for using vancomycin as first line in some ases for RCDAD. Adding S boulardii to vancomycin or metronidazole from the first or second relapse and using pulse/tapering vancomycin therapy have been beneficial in decreasing the relapse rate. For patients with RCDAD, vancomycin therapy followed by rifaximin for two weeks looks promising. New therapies with, nitazoxanide, tinidazole, tiacumicin, rifaximin and ramoplanin are being evaluated and future reports and trials will show their efficacy. Immune therapy is also a promising option treatment in evaluation, showing seroconversion and protective antibody levels in initial tests in healthy volunteer. Passive immunization is also considered but for all these new therapy options, further randomized studies are needed. Prevention is also very important in controlling this disease: first by limiting the use of broad spectrum antibiotics and secondly by controlling the environmental spreading through gloves, handwashing and disposable thermometers.