Healing of skin wounds of the lower extremities can be complicated by concomitant vascular disease. Dysfunction of the arterial, venous, and/or lymphatic systems can compromise the healing of skin ulcers of the legs, creating a burden for patients from painful, draining wounds and placing patients at risk for infection, amputation, and even death. Insights into vascular pathophysiology and an understanding of the processes of wound healing permit an evidence-based approach to patients with vascular leg ulcers. Clinical trials have demonstrated opportunities to improve the care of patients with vascular leg ulcers, thereby reducing morbidity and mortality and easing patients’ burdens.