VLUs represent 90% of lower extremity ulcers. They affect 1 % of the general population and 2.2% of the Medicare population. That same incidence is seen in Europe where 1 % of the population is affected. The incidence is 4 times as high in underdeveloped countries. Recent discoveries have helped better define the chronic nature of venous ulcer pathophysiology. Applying recently developed key concepts in a venous ulcer treatment plan may bring about improved healing outcomes. Important clinical considerations include the effective management of biofilm, control of protease levels, and the role of high-density ECM collagen in healing. For the practitioner, having a better understanding of pathophysiology and using a goal-directed treatment plan can be helpful in delivering quality outcomes for patients with VLUs. With the goal of improving outcomes for this patient population, this article provides awareness of key concepts directed at a modern pathophysiological approach for managing VLUs.