The contraction of granulation tissue from skin wounds was first described in the 1960s. Later it was discovered that during tissue repair, fibroblasts undergo a change in phenotype from their normal relatively quiescent state in which they are involved in slow turnover of the extracellular matrix, to a proliferative and contractile phenotype termed myofibroblasts. These cells show some of the phenotypic characteristics of smooth muscle cells and have been shown to contract in vitro. In the 1990s, a number of researchers in different fields showed that myofibroblasts are present during tissue repair or response to injury in a variety of other tissues, including the liver, kidney, and lung. During normal repair processes, the myofibroblastic cells are lost as repair resolves to form a scar. This cell loss is via apoptosis. In pathological fibroses, myofibroblasts persist in the tissue and are responsible for fibrosis via increased matrix synthesis and for contraction of the tissue. In many cases this expansion of the extracellular matrix impedes normal function of the organ. For this reason much interest has centered on the derivation of myofibroblasts and the factors that influence their differentiation, proliferation, extracellular matrix synthesis, and survival. Further understanding of how fibroblast differentiation and myofibroblast phenotype is controlled may provide valuable insights into future therapies that can control fibrosis and scarring.