Mast cells are known to be the effector cells of immediate-type allergy, but experimental evidence obtained during the last decade has revealed their role in innate and acquired immunity. Upon activation mast cells can undergo an anaphylactic or piecemeal degranulation or degranulation-independent mediator secretion, resulting in rapid or slow release of soluble mediators, such as serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and growth factors. Mast cells can express different receptors and ligands on the cell surface, molecules that can activate the cells of the immune system, such as different subsets of T cells. All these mediators and cell surface molecules can promote inflammation in the skin. During the last years, a new role for mast cells has emerged; induction of tolerance or immunosuppression and interaction with regulatory T cells. However, the mechanisms that switch the proinflammatory function of mast cells to an immunosuppressive one are unknown. In this review, the immunoregulatory function of mast cells and its relation to skin inflammation are discussed.