Massive cell migration, proliferation, phenotypic differentiation, and enhanced biosynthetic activities characterize the sites of wound healing and fibrosis. Regulation of cellular functions by extracellular matrix, which consists of a dynamic assemblage of a variety of interacting molecules capable of reorganization in response to endogenous and exogenous stimuli, represents a fundamental epigenetic mechanism regulating cellular behavior and phenotype. Interactions of the individual components of extracellular matrix with specific cell surface molecules, integrin receptors, and proteoglycans initiate a cascade of signal transduction leading to varied short-term or persistent cellular responses. Extracellular matrix also serves as an important reservoir of cytokines and growth factors, thus modulating the action of a host of potent biological response modifiers by their selective, local accumulation and release. Currently known mechanisms by which extracellular matrix modulates different facets of the process of tissue remodeling after injury, which culminate either in normal wound repair or fibrosis, are discussed.