Escin, hydroxyethylrutoside (HR), and Daflon have been shown to be safe and effective for the treatment of chronic venous insufficiency (CVI). They seem to work differently than compression therapy, suggesting that they would usefully augment this therapy. All three phlebotonics attenuate the drop in adenosine triphosphate in venous endothelial cells during hypoxia. This attenuates (1) the inflammation response, (2) the attraction of neutrophils, (3) damage to the veins, and (4) the release of growth factors. These factors otherwise would perpetuate venous insufficiency and contribute to varicose veins. Additional independent effects that would be useful for the treatment of CVI are that they reduce permeability and fragility; HR, Daflon, and perhaps escin increase venous tone; escin inhibits hyaluronidase; Daflon and probably HR are attracted to the veins. With regard to similarity, no differences in effect have been established among these phlebotonics.