Glyphosate-resistant Palmer amaranth is considered the most troublesome weed in agronomic crops in the Midsouth. The reliance on multiple herbicide mechanisms of action (MOA) and soil-residual herbicides has increased over the past several years due to the ever growing issue of herbicide-resistant weeds. Field experiments were conducted at several locations in Arkansas to determine the efficacy of fluridone on Palmer amaranth in glyphosate-resistant and glufosinate-resistant cotton herbicide programs and to determine the length of residual fluridone activity when applied preemergence (PRE). Fluridone has a unique MOA and is currently not registered as a stand-alone herbicide for use in cotton. In the length of residual experiment, when rainfall was adequate, fluridone applied PRE at rates greater than 224 g a.i. ha-1 provided > 90% Palmer amaranth control for 6 wk after application; however, effective season-long Palmer amaranth control was not achieved with any rate of fluridone alone. Fluridone alone applied 14-d preplant or PRE did not provide greater Palmer amaranth control than a standard herbicide application. When fluridone was integrated into a glufosinate-based herbicide program, PRE-applied fluridone at 224, 336, and 448 g ha-1 did not provide greater Palmer amaranth control than the standard herbicide program that included fluometuron. Based on these experiments, fluridone should not be applied as a stand-alone herbicide in cotton, nor will it reduce the number of POST applications needed for effective Palmer amaranth control in glufosinate-resistant cotton.