Mannose-binding lectin (MBL) is a pattern-recognition molecule that binds to characteristic carbohydrate motifs present on the surface of many different pathogens. MBL binding stimulates the immune system via the lectin pathway of complement activation. In certain clinical situations, often characterized by pre-existing immune compromise, MBL deficiency increases the risk of infectious and other disease-specific complications. Many of the key pathogenic processes inherent to common gastroenterological diseases, such as infection, immunological damage, and carcinogenesis, have been linked to MBL. This editorial reviews the biology of MBL, outlines key disease associations to document the breadth of influence of MBL, and finally, highlights the relevance of MBL to both gastroenterological health and disease.