The Roundup Ready Flex system is a new transgenic weed control technology developed by Monsanto that should provide improved reproductive tolerance in cotton to over-the-top applications of glyphosate. Several studies were conducted in South Carolina over the past few years to determine the performance and adaptability of this new technology in South Carolina. Specific objectives were: to determine yield reductions in Roundup Ready Flex cotton systems directly associated with delayed applications of glyphosate during reproductive development and indirectly from early-season weed interference associated with delayed glyphosate applications; to compare lint yields, weed management costs, and net profit for Roundup Ready Flex weed management systems with conventional herbicide systems; and to evaluate the performance of new varieties containing the Roundup Ready Flex technology (both unsprayed and sprayed over-the-top with glyphosate) in South Carolina.