Clostridium difficile infection (CDI) is the leading cause of nosocomial diarrhoea in older people, causing substantial morbidity and mortality. The fact that CDI is almost exclusively a disease of older people and the debilitated indicates that patient susceptibility is a major determinant of who gets CDI. It would help efforts to combat this disease if we better understood and could reduce patient susceptibility. In this regard, several strategies are currently under investigation. The use of probiotics for CDI has received particular attention in the medical and lay media. Patients and their carers often ask doctors about them. In this review article, we describe the pathogenesis of CDI before looking at the ageing host in more detail. We discuss how probiotics may work and review the current evidence for their use in CDI.