In 2004 and 2005, glyphosate + diuron and flumioxazin + MSMA were applied POST-directed to cotton at 20, 30, 40, and 50 cm in height. Herbicides were directed to either the lower 2 cm of the cotton stem or to the lower 50% of the cotton stem to determine the impact of application timing and placement on cotton response. Glyphosate + diuron resulted ≤ 22% injury when applied high on the stem and ≤ 8% injury when applied low on the stem. Regardless of application placement or timing, no yield reductions were observed as a result of glyphosate + diuron application. Conversely, flumioxazin + MSMA applications resulted in 93 and 64% injury when applied high POST-directed (HPD) to 20- and 30-cm cotton, respectively. Low POST-directed (LPD) applications caused 33 and 23% injury to 20- and 30-cm cotton, respectively. In both years, HPD applications of flumioxazin + MSMA on 20-cm cotton resulted in excessive yield loss (94 to 87%), whereas yield loss was only noted in 30-cm cotton in 2004. No yield loss was observed in 40- or 50-cm cotton. Additionally, LPD applications of flumioxazin + MSMA, though causing significant visual injury, did not result in a yield reduction at any application timing. Although cotton became more tolerant to flumioxazin + MSMA as the season progressed, the research suggests that applications of flumioxazin should be made with precision or delayed until cotton reaches 40 cm in height.