Myofibroblasts are unique mesenchymal cells with properties inherent to both muscle and nonmuscle cells. They are widely distributed in embryos, are essential for the formation of functional adult tissues, and are intimately involved in tissue homeostasis and wound healing. Cytoskeletal protein expression and contractile properties distinguish them from other cell types. Myofibroblasts also express skeletal muscle structural and regulatory proteins, including sarcomeric myosin heavy chain and MyoD. Despite the presence of such myogenic regulatory proteins, these cells do not terminally differentiate into skeletal muscle. This article focuses on the interesting biology of myofibroblasts, their origin, and the molecular mechanisms that allow these cells to maintain a state intermediate between muscle and nonmuscle cells.