Chronic venous diseases of the lower extremities have classic multifactorial etiology including the interaction between the external factors and the structural features of a large number of genes. Despite the high prevalence of these diseases, our knowledge of the molecular mechanisms underlying their pathogenesis is extremely scarce. At the heart of the development of pathological processes, there may be even mechanical factors that trigger a complex cascade of cellular reactions that may subsequently be amplified by genetic factors. The genes involved in the primary venous pathology remain elusive and the magnitude of the genetic contribution to the disease phenotype is yet to be clarified. The current review is focused on the genetic components of such chronic venous diseases as varicose veins and chronic venous insufficiency with special reference to their most severe clinical outcome in the form of venous ulceration. For a number of reasons, many studies subjected to the analysis provide conflicting evidence about the clinical relevance of genetic associations. The multicenter international studies involving a number of populations of the patients matched in terms of the inclusion and exclusion criteria and investigating the same range of genetic markers taking into consideration the ethnic aspects would be instrumental in clarifying the relationship between different pathological conditions associated with chronic venous diseases and their genetic components. The present work is an attempt to critically review and analyze the literature publications reporting the studies on the genetic components of varicose vein disease, chronic venous insufficiency, and venous ulcers in the lower extremities. Moreover, the information summarized in this article and presented in a concise form may be of value for the clinicians and further used in modern phlebological practice.