Venous leg ulcers are common and cause considerable morbidity in the population. As healing may be slow or may never be achieved, ulcers create persistent and substantial demands on clinical resources. Great efforts have been made to accelerate tissue repair in chronic venous leg ulcers with limited success. This may at least be partly due to the limited knowledge on the microenvironment of chronic wounds. In fact, the tremendous impact of the microenvironmental conditions on the outcome of wound healing has increasingly become apparent. Oxidative stress as a consequence of an imbalance in the prooxidant‐antioxidant homeostasis in chronic wounds is thought to drive a deleterious sequence of events finally resulting in the nonhealing state. The majority of reactive oxygen species are most likely released by neutrophils and macrophages and to an unknown extent from resident fibroblasts and endothelial cells. As the inflammatory phase does not resolve in chronic wounds, the load of reactive oxygen species persists over a long period of time with subsequent continuous damage and perpetuation of the inflammation. In this article, we will critically discuss recent findings that support the role of oxidative stress in the pathophysiology of nonhealing chronic venous leg ulcers.