Horse chestnut seed extract (HCSE) is widely used in Europe for the management of chronic venous insufficiency (CVI). Although traditionally recommended for a variety of medical conditions, CVI is the only indication for which there is strong supportive scientific evidence. Review of the literature reveals 14 randomized controlled trials, of which seven are methodologically of high quality, albeit limited by small sample sizes and short durations. These studies support the superiority of HCSE over placebo, and suggest equivalence to compression stockings and to oral oxerutins. In the future, a longer and adequately powered randomized trial is warranted to compare HCSE to standard of care, and to further assess safety and long-term efficacy. There are no data to suggest that horse chestnut flower, raw seed, branch bark, or leaf are effective for any indication, and it is recommended that these products not be used, as they are known to be toxic when ingested.