Roundup Ready cotton was introduced in 1997. This technology was the direct result of genetically engineering cotton cultivars with in-plant vegetative tolerance to the herbicide glyphosate. Roundup Ready cotton cultivars are tolerant to glyphosate applications through the four-leaf stage. After the four-leaf stage, the tolerance level to topical applications is decreased and reproductive problems such as malformed bolls due to poor pollination or immature boll shed may occur. Therefore applications of glyphosate to Roundup Ready cotton must be post-directed after the fifth true leaf reaches the size of a quarter.

Roudup Ready Flex cotton, commercialized in 2006, is a result of a similar genetically engineered process utilizing the same gene with a new transformation event and a different promoter. The result is cotton culltivars with increased tolerance to glyphosate during both reproductive and vegetative stages, thus widening the window for topical glyphosate application. Research with Roundup Ready Flex technology has concluded that topical applications of glyphosate can be made throughout the cotton growing season without resulting in malformed bolls or yield loss.