Clostridium difficile infection (CDI) is a potentially fatal illness with an increasing incidence worldwide. Despite extensive ongoing research into CDI treatment, management of CDI still poses important problems, such as a high propensity to relapse and refractoriness to treatment, especially when there is an ileus and oral drugs cannot be administered. This guideline evaluates the available literature, discusses criteria for disease severity and provides recommendations for CDI treatment, indicating level of evidence and strength of recommendation.