This paper focuses on Ruscus aculeatus extract (Ruscus extract) and its combination with hesperidin methyl chalcone (HMC) and ascorbic acid (AA), which have been safely and effectively used in CVD treatment for more than 50 years in some European countries. It presents the effects of that drug on veins and on venous hypertension, its effect on microcirculation and on lymphatics demonstrated by preclinical studies and the clinical evidence issued from clinical trials supporting its use to relieve the symptoms of venous disease. In addition to its venoconstrictive effect on veins, its pharmacological action is on the microcirculation impairment caused by venous hypertension that is at the heart of the pathophysiological mechanism underlying venous disease.