Background:Chronic venous insufficiency (CVI) is a prevalent disease traditionally managed with compression, lifestyle change and surgical/endovenous interventions. Venoactive drugs (VADs) have emerged as important adjunctive therapies. This review evaluates the mechanisms of action, clinical efficacy, and evidence supporting pharmacological therapies for CVI. Methods:A narrative review of guidelines, systematic reviews, and published studies was undertaken to assess established and emerging pharmacological agents used in the management of CVI. Results:Current guidelines support the use of several VADs, including micronized purified flavonoid fraction (MPFF), Ruscus extract, calcium dobesilate, horse chestnut extract, hydroxyethyl-rutosides, red vine leaf extract, and sulodexide. These agents predominantly act by improving venous tone, reducing capillary permeability, enhancing microcirculation, and attenuating inflammatory pathways. Clinical benefits are mainly symptomatic. Among these agents, MPFF and sulodexide possess the strongest evidence base. Additional therapies with emerging evidence include pentoxifylline, statins, aminaphtone, pycnogenol, and Centella asiatica. Pentoxifylline may enhance venous ulcer healing, while statins have shown potential disease-modifying effects through inhibition of venous wall inflammation and remodelling. However, evidence for these newer therapies remains limited by small sample sizes, study heterogeneity, and insufficient long-term data. Conclusions:VADs play a valuable role primarily through symptomatic improvement and promotion of ulcer healing. These agents should be considered complementary to, rather than replacements for, compression therapy. Despite promising results, widespread guideline adoption is constrained by variability in study quality and limited long-term evidence. Further large-scale, high-quality trials are required to clarify efficacy, safety, and potential disease-modifying effects of VADs.