Clostridium difficile infection is not new, but it is posing more problems than ever before, described by the Centers for Disease Control and Prevention as an urgent threat. Its pathophysiology allows C difficile to be very difficult to manage, both within the hospital environment and in a patient’s body. This article reviews clinical manifestations of the infection, outlines both medical and surgical treatment options, and discusses risk factors and predictors. Implications for nurses are thoroughly described. The epidemic proportion of C difficile infection gives cause for serious concern, especially for vulnerable populations, such as adults over age 65.