This review paper discusses the mechanism of development of venous pathology and the therapeutic options of sulodexide in venous disease. Chronic venous insufficiency (CVI) is a common pathologic process involving the lower extremities, which presents with diverse clinical findings. The hallmark of the pathologic process is the development of increased venous pressure, which in turn leads to microcirculatory changes. These changes manifest as hypertrophy of the capillaries and endothelial dysfunction. The endothelial dysfunction is accompanied by release of inflammatory mediators as well as a change in the fibrinolytic system, which restricts the skin perfusion. The restricted perfusion, in conjunction with inflammation, is responsible for the development and poor healing of venous ulcers. Sulodexide is a specific glycosaminoglycan (GAG) that consists of 80% fast moving heparin and 20% dermatan sulphate and has a unique pharmacological and therapeutic profile. Sulodexide has been shown to reverse the endothelial dysfunction and restore the fibrinolytic balance and is an important adjunct in treating the manifestations of CVI. It also has substantial antithrombotic properties without significantly increasing the risk of haemorrhage. Oral administration of sulodexide is safe and effective since there is no interaction with other drugs. The therapeutic options of sulodexide include CVI, superficial and deep venous thrombosis, and improved healing of venous ulcers.