Clostridium difficile is well recognized as the most common infectious cause of healthcare-associated diarrhea. Since 2000, this pathogen has demonstrated an increased propensity to cause more frequent and virulent illness that is often refractory to treatment. An analysis by the Centers for Disease Control and Prevention revealed that, in the United States, the number of patients discharged from hospitals who received the International Classification of Diseases, Ninth Revision discharge diagnosis code for C. difficile infection (CDI) more than doubled from 2000 to 2003. Unpublished data indicate that this trend has continued and that more than 250,000 US hospitalizations were associated with CDI in 2005. A previously uncommon hypervirulent strain of C. difficile is thought to contribute, in part, to the dramatic increase in the incidence and severity of the infection. Although the economic impact of the disease is believed to be profound and is expected to increase, data on the costs associated with CDI are scarce. To more completely assess its economic burden, we performed a review of available literature that reported costs associated with the infection.