The upright posture of man had been a major evolutional challenge. The mechanisms responsible for orthostatic tolerance mostly affect the venous system. In this paper, we discuss new results regarding the biomechanics of the venous system highlighting a rather neglected field, the biomechanical properties of the vein wall. These properties change according to localization of veins, age, gender and body mass. The anti-gravitational adaptation of veins is a complex process involving all three layers of the venous wall. Local myogenic and humoral mechanisms as well as systemic hormonal and nervous influences control the adaptive processes in the veins. Long term adaptation involves structural and functional remodeling of the venous wall. Disorders of the veins mostly cause pathological remodeling. Hemodynamic factors (pressure and flow) together with inflammatory processes may lead to pathological alterations, changing the biomechanical properties of the vein wall, which further contribute to the reservation and progression of venous dysfunction. Appropriate testing of venous function can reveal biomechanical disorders even in clinically asymptomatic patients. Thus, biomechanical investigation of veins not only helps to understand the underlying pathomechanism but it also can contribute to early diagnosis and follow-up of venous disorders. When recognized in time, pathological remodeling can be prevented or treated. In this way, the incidence of venous disorder could be cut back reducing both human suffering and material loss.