Clostridium difficile associated disease is a well recognized nosocomial infection evolving as a severediarrheal illness, associated with significantly higher rates of morbidity and mortality in critically ill patients. The incidence of Clostridium difficile infection is higher and its impact is more severe in trauma patients when compared with general inpatient population. There are several potential diagnosis tools for Clostridium difficile colitis, however choosing the right diagnostic approach is a difficult task, especially in trauma patients in whom a rapid and certain diagnosis is of paramount importance. Moreover, managing these patients may prove to be a very challenging task, considering the emergence of novel aggressive Clostridium difficile strains resulting in increased disease severity.