In this issue of Gastroenterology Clinics, guest editor Dr. R. Balfour Sartor brings his considerable expertise to the topic of The Microbiome. Research on the gut microbiome has revealed significant implications for gastrointestinal diseases, with clinical trials resulting in potential treatments for the management of GI diseases and their associated risk factors. Further, understanding the gut microbiome’s role in gastrointestinal health opens avenues for targeted interventions and personalized approaches to disease management. This issue presents the latest research, treatments, and clinical approaches in this key area of gastroenterology.