Micronized purified flavonoid fraction (MPFF) is a flavonoid-based venoactive drug that is more potent than pure diosmin due to the presence of additional flavonoids, such as hesperidin, diosmetin, linarin, and isorhoifolin. In addition, the dissolution and absorption rates of MPFF increase due to the micronization of its active ingredients. The micronization process improves exposure to MPFF-derived metabolites that are responsible for its pharmacological activity. The positive impact of micronization on the pharmacological activity of purified flavonoid fraction has been demonstrated in both animal and clinical pharmacological trials. MPFF improves venous tone by modulating noradrenergic signaling and reducing norepinephrine metabolism and MPFF also protects against inflammation-related valve damage by inhibiting the leukocyte-endothelium interaction, decreasing capillary permeability, improving capillary resistance, and increasing lymphatic drainage. The best dose-effect ratio is achieved with 1000 mg. MPFF is an important treatment option for chronic venous disorders because it relieves symptoms at all stages, significantly alleviates venous edema, and, in more advanced stages, MPFF may be used in conjunction with sclerotherapy, surgery, and/or compression therapy for patients undergoing stripping or an endovenous operation for varicose vein ablation. MPFF may also be used as an adjunctive therapy in patients with active venous ulcers, especially in patients with chronic large ulcers.