Clostridium difficile Associated Diarrhoea (CDAD) is the leading cause of nosocomial diarrhoea. Clostridium difficile Infections (CDIs) may be induced by medication or medical procedures that disrupt normal bowel flora or interfere with bowel motility. The emergence of hyper-virulent strains of CDI, reports of severe or recurrent CDI in immunocompetent populations, advent of various infection control challenges, and diagnostic and therapeutic dilemmas have contributed to a shift in the disease paradigm. However, there is insufficient data on the risk of CDI in vulnerable cancer patients receiving chemotherapy or who are admitted to health care settings for long periods of time. This review describes the epidemiology, risk factors, pathophysiology, and management of CDIs in cancer patients receiving chemotherapeutic agents.