Mast cells play a central role not only in type I hypersensitivity reactions, but also in chronic inflammatory processes resulting in fibrosis. Fibrosis is a process characterized by fibroblast proliferation and/or by excessive production and deposition of collagen and other extracellular matrix components. The close proximity of mast cells and fibroblasts in the connective tissue enables the interaction between these two cell types. Fibroblasts have been shown to provide the microenvironment for connective tissue mast cell differentiation and survival. On the other hand, mast cells can affect fibroblasts through the release of various mediators with either fibrogenic or fibrolytic activities. Mast cells were shown to be present in active form in various fibrotic conditions such as scleroderma, chronic graft-versus-host disease, eosinophilic fasciitis, wound healing, idiopathic pulmonary fibrosis, and ocular cicatricial pemphigoid. This review presents the current data about mast cell and these fibrotic disorders.