Resistance to the herbicide glyphosate is currently known in at least eight weed species from many countries. Some populations of goosegrass from Malaysia, rigid ryegrass from Australia, and Italian ryegrass from Chile exhibit target site-based resistance to glyphosate through changes at amino acid 106 of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene. Mutations change amino acid 106 from proline to either serine or threonine, conferring an EPSPS weakly resistant to glyphosate. The moderate level of resistance is sufficient for commercial failure of the herbicide to control these plants in the field. Conversely, a nontarget site resistance mechanism has been documented in glyphosate-resistant populations of horseweed and rigid ryegrass from the United States and Australia, respectively. In these resistant plants, there is reduced translocation of glyphosate to meristernatic tissues. Both of these mechanisms are inherited as a single, nuclear gene trait. Although at present only two glyphosate-resistance mechanisms are known, it is likely that other mechanisms will become evident. The already very large and still increasing reliance on glyphosate in many parts of the world will inevitably result in more glyphosate-resistant weeds, placing the sustainability of this precious herbicide resource at risk.