Roundup Ready Flex^TM (RRF) cotton technology provides a significant advantage over the original Roundup Ready^TM technology released for commercial production in 1997. RRF technology provides producers the ability to apply glyphosate over-the-top of RRF cotton from the cotyledon stage until seven days prior to harvest allowing for effective control of later season weed escapes. Research presented herein investigates the optimum time of weed removal and the effect of multiple applications of glyphosate on RRF cotton. Research was conducted using traditional small plot techniques. Evaluation of weed control, cotton response, and lint yield were utilized to determine the most effect timing and number of glyphosate applications.