In this issue of Infectious Disease Clinics of North America, guest editor Dr. Vincent B. Young brings his considerable expertise to the topic of Clostridioides difficile Infection. In the last decade there have been major changes in the diagnosis, epidemiology, and treatment of this important nosocomial infection. New treatments including new antibiotics and monoclonal antibodies have been developed to treat both initial episodes and recurrent CDI, and diagnostic and treatment guidelines have been created to reflect these developments. This issue addresses these changes to the clinical prevention, diagnosis, and treatment of CDI and also touches on advances in basic science that are more directly relevant to clinicians who encounter CDI in their daily professional practice.