Approximately one third of patients admitted to the ICU develop diarrhea during their hospitalization. Diarrhea can lead to further complications, such as volume depletion and wound infection, and can significantly increase medical costs. The most common causative factors are medications, enteral feedings, and C. difficile infections. These may be implicated alone or in combination. Further investigations of the pathophysiology of ICU diarrhea as well as potential therapies are needed to clarify the proper approach to this important and complex problem.