Summary: Observations of increased numbers of mast cells at sites of chronic inflammation have been reported for over a hundred years. Light and electron microscopic evidence of mast cell activation at such sites, taken together with the known functions of the diverse mediators, cytokines, and growth factors that can be secreted by appropriately activated mast cells, have suggested a wide range of possible functions for mast cells in promoting (or suppressing) many features of chronic inflammation. Similarly, these and other lines of evidence have implicated mast cells in a variety of adaptive or pathological responses that are associated with persistent inflammation at the affected sites. Definitively characterizing the importance of mast cells in chronic inflammation in humans is difficult. However, mice that genetically lack mast cells, especially those which can undergo engraftment with wildtype or genetically altered mast cells, provide a means to investigate the importance of mast cells and specific mast cell functions or products in diverse models of chronic inflammation. Such work has confirmed that mast cells can significantly influence multiple features of chronic inflammatory responses, through diverse effects that can either promote or, perhaps more surprisingly, suppress aspects of these responses.