The incidence of Clostridium difficile infection (CDI) continues to rise, whilst treatment remains problematic due to recurrent, refractory and potentially severe nature of disease. The treatment of C. difficile is a challenge for community and hospital-based clinicians. With the advent of an expanding therapeutic arsenal against C. difficile since the last published Australasian guidelines, an update on CDI treatment recommendations for Australasian clinicians was required. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children.