The name myofibroblast was proposed several years ago for fibroblastic cells located within granulation tissue and exhibiting an important cytoplasmic microfilamentous apparatus [1, 2]. The suggestion that these cells are responsible for the phenomenon of wound contraction was rapidly taken into consideration because about the same time the concept that any cell, and not only muscle cells, is provided with a contractile apparatus responsible for the regulation of such phenomena as cell shape modulation or cell motility was becoming more and more popular (for review see [3]). Several laboratories have reported the presence of cells with myofibroblastic features during a variety of pathological situations [3] and also in normal tissues, where they could exert a mechanical function (for review see [4]). Table 1 lists the locations of myofibroblasts in normal tissues. Later, it was observed that the microfilamentous apparatus of myofibroblasts contains actin and myosin and in particular α-smooth muscle (SM) 2 actin, the actin isoform typical of SM cells located in the vessel wall [5]. α-SM actin became the most reliable marker of myofibroblastic cells. It was also discovered that myofibroblasts could express several other SM cell markers according to the pathological situation and/or to the location [6]. Hence, the proposal was made that a spectrum of phenotypes exists between fibroblastic and SM cells [7]. The modulations within this spectrum are probably controlled by a local network, including growth factors, cytokines, adhesion molecules, and extracellular matrix (ECM) components. The purpose of this review is to summarize the most recent achievements in the understanding of:(1) the role of contractile proteins, α-SM actin in particular, in the production of retractile and fibrotic phenomena and (2) the local factors controlling the modulation and activity of myofibroblasts.