Studies were conducted at Clayton, Goldsboro, and Rocky Mount, NC, to evaluate weed and cotton response to herbicide programs in glyphosate-resistant cotton. Just prior to cotton harvest, programs containing norflurazon, trifluralin, fluometuron, glyphosate, MSMA, cyanazine, and/or pyrithiobac in various combinations controlled common lambsquarters, common ragweed, goosegrass, ivyleaf morningglory, and smooth pigweed at least 94%. Glyphosate-resistant cotton injury was no more than 5%. Yields for glyphosate programs differed only at Clayton, where glyphosate programs containing residual herbicides yielded more than glyphosate alone. Depending on location, programs utilizing glyphosate as needed required a minimum of two and a maximum of four applications to prevent yield loss when minimal soil-applied herbicides were used. Other as-needed programs required one-three glyphosate applications, depending on location. For comparison based on application, herbicide, and adjuvant costs, the standard program of trifluralin preplant incorporated (PPI), pyrithiobac postemergence (POST), and fluometuron plus MSMA postemergence-directed (PD) was $119/ha compared with trifluralin PPI followed by (fb) two applications of glyphosate ($54/ha) or four applications of glyphosate ($94/ha).