Clostridium difficile infection (CDI) is an increasing problem in hospitalized patients. Recurrences of disease, despite the recommended treatments with metronidazole or vancomycin, are frequently seen and pose major problems for the clinical management of patients with CDI. Evidence for efficient clinical cure and low recurrence rates with primary use of alternative antibacterial treatment, such as fidaxomicin and rifaximin, is growing and these treatment strategies need further exploration. The use of probiotics (e.g. Saccharomyces boulardii) may be considered, as well as combination therapy with vancomycin. Other promising therapies are the use of (monoclonal) antibodies and faecal transplantation, the efficacy of which has been suggested in smaller studies. Large studies evaluating faecal transplantation and other microbial products are underway. This article focuses on recurrent CDI and the possibilities for treatment and reduction of recurrence rates. Furthermore, general concepts of CDI and the primary treatment strategies are discussed. In summary, recurrent CDI remains a challenging clinical entity for which more treatment options will be forthcoming in the next few years.