Clostridium difficile infection (CDI) is increasingly common, and it is associated with significant morbidity, mortality, and cost burden for patients and the healthcare system. The severity and rates of recurrent CDI and associated mortality are also increasing. This article is an overview of the changes in CDI epidemiology that have occurred since the turn of the century and the current scope of the problem. The 3 articles that follow in this supplement address the diagnosis and treatment of initial and recurrent CDI, and current practice guidelines for the prevention and control of CDI in the hospital setting. Journal of Hospital Medicine 2012;7:S1–S4. © 2012 Society of Hospital Medicine