Mast cells are best known for their potent effector functions in allergic disorders. In recent years, however, mast cells have been identified to be involved in a surprisingly complex range of immune functions that go far beyond allergies and include the development of autoimmune disorders and peripheral tolerance, and the initiation and maintenance of adaptive and innate host responses. Here, we review the key signals and effector mechanisms that have lately been identified for mast cell functions in these immune responses.