A field study was conducted in Yuma, Arizona during the late fall 2001 growing season to determine the optimum postemergence (POST) timing of glyphosate application on glyphosate- tolerant Lactuca sativa (head lettuce) for weed control. Head lettuce cv. Raider demonstrated excellent tolerance and no injury was observed on the crop after any glyphosate application at the 2, 4, 6, or 8 leaf stage of growth. A single application of glyphosate at 1.0 lb AI/A at the 4 or 6 leaf stage of lettuce growth was optimal for providing near complete control of Portulaca oleracea (common purslane), Chenopodium album (common lambsquarters), C. murale (nettleleaf goosefoot), Physalis wrightii (Wright’s groundcherry), volunteer cantaloupe (Cucumis melo), and Echinochloa colonum (junglerice). An early application at the 2 leaf stage resulted in few new weeds emerging after the application. A later application at the 8 leaf stage resulted in reduced yields of lettuce fresh weight due to weed competition. POST applications of glyphosate on lettuce offered superior weed control compared to soil-applied preemergence (PREE) herbicide treatments.