Glyphosate is the only herbicide used for controlling illicit coca (Erythroxylum coca and E. novogranatense), a source of cocaine. Because commercially available formulations of glyphosate were inconsistent in controlling coca, research was conducted in a large-scale aerial eradication program, greenhouse (in Maryland) and field (Hawaii), to develop more effective control systems. Sixteen surfactants (cationic, nonionic, or mixed) were tested with two commercial glyphosate herbicide formulations, in aqueous or oil-based carrier systems, for coca control. Ultimately, two glyphosate–surfactant systems (COC/OSI-U [a mixture of crop-oil concentrate, Agri-Dex® and organosilicone, Silwet L-77®] and CAT/ANA [cationic surfactant/anionic surfactant, Optima®]) were found that increased glyphosate phytotoxicity fourfold: 1.1 kg ae/ha of glyphosate + surfactant was equivalent to 4.4 kg ae/ha glyphosate without added surfactant, for both species. In consequence, the glyphosate mixture used in Colombia for coca eradication was modified with substantially improved results.