Cell behavior is determined by both genetic and environmental factors. Cell microenvironment is not only a scene where different actors play a role, but it is himself an active participant in the scenario, able to influence many cellular responses by binding signaling molecules or by modulating intracellular signaling cascades. Further, extracellular matrix remodeling is a critical step to permit physiological as well as pathological processes. As environmental factors are able to modulate gene expression by epigenetic modifications, this review will focus on new aspects of the regulation of extracellular matrix remodeling enzymes. Moreover, as one of the main components of cell microenvironment is the glycosaminoglycan hyaluronan, novel findings in the control of hyaluronan synthesis will be discussed in terms of epigenetics and post-translational point of view.This article is protected by copyright. All rights reserved.