Mast cells have been considered for many years to participate specifically in allergic reactions through the release of cytokines, chemokines, proteases, leukotrienes, and bioactive polyamines. Emerging roles for mast cells have been identified recently, which highlight their relevance in both innate and adaptive immunity. Mast cells play a role in many different processes, including clearance of enteric pathogens, food allergies, visceral hypersensitivity, and intestinal cancer. The activation of mast cells can initiate inflammatory reactions that are life-saving in some circumstances (eg, nematode infection) but life-threatening in others (eg, allergy). In recent years, mast cells, their products, and the mechanisms by which mast cell activity can be regulated by the microenvironment are a major area of investigation. The purpose of this review article is to summarize and highlight the latest findings in mast cell biology associated with intestinal homeostasis and pathologies.