Mast cells are not only potent effector cells in allergy, but are also important players in protective immune responses against pathogens. Most of our knowledge about mast cells in innate immunity is derived from models of sepsis, whereas their role in innate immune responses of the skin has largely been neglected in the past. Their particular pattern of distribution in the skin and their ability to sense and react to pathogens and other danger signals indicate that mast cells can be important sentinels and effector cells in skin immune responses. The recent findings reviewed here have confirmed this hypothesis and have established a prominent role for skin mast cells in innate immunity.