BACKGROUND Sclerotherapy is popular for the treatment of lower extremity telangiectasias and varicose and reticular veins. Although a large number of sclerosants are commonly employed, there are few data that directly compare their advantages and drawbacks. OBJECTIVES To analyze and present the differences between sclerosants that make them more or less suitable agents in specific clinical applications. MATERIALS AND METHODS A systemic review of published medical literature that compares and contrasts different classes of sclerosants is presented. RESULTS There is no perfect sclerosant that is complication free and 100% effective. The ability to match the sclerosant to the clinical problem being approached makes the availability of more Food and Drug Administration–approved sclerosants appealing. CONCLUSION Modern sclerosants that have been subjected to rigorous experimental and clinical trials will provide even more efficacious and safer patient treatments. David M. Duffy, MD, received a grant from Bioform for support of this article.