Chronic venous disease (CVD) is common. Its manifestations include varicose veins; skin changes such as dermatitis, hyperpigmentation, and lipodermatosclerosis; and chronic leg ulcers. Recent advances in the understanding of its pathophysiology have shown how molecular mechanisms in the inflammatory cascade are involved in these diverse findings. Venous hypertension and associated fluid shear stress alterations on the endothelial surface may initiate this cascade and may lead to adverse changes in the venous wall, venous valves, and skin that can eventually result in varicose veins and in venous ulcers.