Clostridium difficile infection (CDI) is a common problem encountered in solid organ transplant (SOT) recipients and the incidence is increasing. Generally, SOT recipients have an incidence of CDI that is similar to other post-operative patients, but this group has several unique risk factors that may contribute to more severe disease. Recent studies in non-transplant patients have indicated that treatment choices should be based on the severity of the illness. Although there continues to be a lack of well designed, randomized, controlled trials to support the management decisions that must be made for SOT recipients with CDI, the available evidence is reviewed and summarized for these treatment guidelines.