Research was conducted at experimental research stations near Keiser and Marianna (Marianna-A), AR, in 2007, and in a grower's field near Marianna (Marianna-B), AR, in 2008, to compare herbicide programs, including POST application(s) of glyphosate/glufosinate alone or in combination with residual herbicides applied as PRE, mid-POST (MPOST), or layby POST-directed (PD) in enhanced glyphosate- and glufosinate-resistant cotton. Weed species evaluated included Palmer amaranth, pitted morningglory, hemp sesbania, barnyardgrass, and a mixture of large crabgrass and goosegrass. At Marianna-B, AR, the Palmer amaranth population was a mixture of glyphosate-resistant and -susceptible plants. For both cotton cultivars and at all locations, inclusion of S-metolachlor plus fluometuron PRE increased weed control and/or decreased the number of glufosinate or glyphosate applications needed in-season. At Marianna-B, AR, PRE residual herbicides and/or glufosinate were required to control glyphosate-resistant Palmer amaranth. Addition of pyrithiobac to glufosinate or glyphosate did not increase weed control. A layby PD application of flumioxazin plus MSMA was required to increase late-season control of all weed species in POST glufosinate-only programs, but not in POST glyphosate-only programs. None of the programs caused &gt;&amp;#8201;5% injury to either cotton cultivar. Seed-cotton yield was similar in all herbicide programs at Keiser, AR, and Marianna-A, AR, except for the POST glyphosate-only program, which yielded less than the PRE followed by POST programs in glyphosate-resistant cotton at Keiser, AR. In general, PRE herbicides did not increase cotton yield but did improve early and late-season control of glyphosate-susceptible and -resistant weeds in both cotton cultivars.