Clostridium difficile infection (CDI) is a major concern for health care system and clinicians. Interest in C. difficile infection has increased recently due to an ongoing C. difficile epidemic with a hypervirulent strain and mortality. Disease due to C. difficile is responsible for substantial strain on the hospital system by increasing patients length of stay and increasing costs. Present studies have demonstrated chemotherapeutic agents as an independent risk factor for CDI potentially leading towards serious morbidity and mortality. However, the current strategies lack randomized trials on management in chemotherapy-associated CDI. The changing face of the disease, emergence of more resistant strains, and the rising cancer incidence have heightened the need for identification of risk factors, rapid diagnosis including prompt identification of toxins, and management algorithms. This review focuses on recent insights on the epidemiology, diagnosis, current management, recent patents, and advances on treating strategies of CDI with reference to current studies.