Field experiments were established in Lee Co. South Carolina to evaluate coffee senna control in cotton with commercially available preemergence (PRE), early postemergence directed (EPD), and late postemergence directed (LPD) herbicides and with DPX-PE350 (Staple) applied PRE, early postemergence over-the-top (EPOT), and PRE followed by (fb) EPOT. Early postemergence treatments were applied when cotton and coffee senna seedlings were 3 to 5 inches and 1 to 3 inches tall, respectively; LPD treatments were applied when cotton was 6 to 10 inches tall and coffee senna was up to 9 inches in height. Preemergence and early postemergence over-the-top (EPOT) treatments were broadcast, whereas postemergence directed treatments were applied on a 20 inch band over the crop row. Preemergence applications of Cotoran (2.0 lb ai/ac) and Zorial (1.5 lb ai/ac) controlled coffee senna 90 and 65%, respectively, 6 weeks after planting (WAP). Probe @ 0.75 lb ai/ac EPD provided 96% control 2 weeks after application whereas, EPD applications of Cotoran (2.0 lb ai/ac) and MSMA (2.0 lb ai/ac) provided 70% and 16% control, respectively. Bladex (0.8 lb ai/ac), Karmex (0.3 lb ai/ac), and Caparol (0.5 lb ai/ac) LPD averaged only 55% control 8 WAP. MSMA (2.0 lb ai/ac) LPD provided 12% control of coffee senna. The ineffectiveness of the LPD treatments was partially attributed to the large size of the coffee senna at application (up to 9 inches) and the lack of a height differential between the cotton and weeds. Sequential applications of Cotoran and Zorial PRE followed by (fb) Probe EPD and Bladex LPD provided 99% control of coffee senna 6 WAP. Staple provided good to excellent coffee senna control 6 WAP (89, 89, and 95% control with PRE, EPOT, and PRE fb EPOT applications, respectively). Lint cotton yields generally reflected the level of weed control. Lint cotton yields were similar to weed-free cotton with all treatments except MSMA EPD and the LPD treatments.