The gastrointestinal mucosa is an extremely soft, highly vascularised tissue, with a single layer of epithelium separating the gut lumen from the host. Epithelial cells adhere to a thin basement membrane that is produced by both epithelial cells and the underlying stromal cells. Signals passing between epithelial cells and stromal cells are needed for normal gut structure. In gut diseases, however, epithelial cells and stromal cells produce large amounts of matrix degrading enzymes (matrix metalloproteinases), the function of which is only beginning to be elucidated. Here, we review the role of matrix metalloproteonases (MMPs) in the gut in health, in gut inflammation, and in cancer.