The emphasis of Roundup Ready technology in both soybean and corn are factors that have contributed to the development of a number of herbicide-resistant weeds in Kentucky and the surrounding region. In addition, the rapid introduction and spread of herbicide-resistant Palmer amaranth and waterhemp across the state has added to this problem, particularly with recent reports and findings that indicate that populations of these weeds may have resistance to multiple herbicide site of action groups [that is, weeds with resistance to more than one herbicide site of action]. Over 90 percent of the U.S. soybean acreage is planted to soybean varieties with glyphosate-resistance, so weeds having resistance to this herbicide present a large challenge to soybean growers. In order to limit the development and spread of weeds with multiple herbicide resistance, scientists emphasize the need to diversify cultural practices and choice of herbicide programs that offer multiple sites of action. Growers are now beginning to utilize soil-residual herbicides combined with postemergence treatments which can be applied on glufosinate [Liberty Link soybean] or dicamba [Roundup Ready 2 Xtend soybean]. A new generation of soybean varieties (eg. Xtend Flex, Enlist E3, and LibertyLink GT27 soybean) are on the horizon and anticipated to be soon available to producers that will be tolerant to glyphosate, glufosinate, dicamba, 2,4-D, and other traits, which could provide additional flexibility in herbicide options to combat Palmer amaranth and waterhemp. RESEARCH DESIGN AND METHODS: Trials were conducted in cooperation with soybean producers in Taylor, Caldwell, and Fulton Counties who had fields with Palmer amaranth and waterhemp infestations. All plots were planted with an Xtend Flex soybean variety (glyphosate-, glufosinate-, and dicamba- resistant) that was sourced from Bayer Crop Science, allowing for all treatments to be applied to one soybean variety. Experiments were conducted in a no-tillage system with all treatments receiving a non-residual burndown at planting. Experiments were laid out in a randomized complete block design with four replications in a factorial treatment arrangement. The factorial design contained two primary factors: 1) Preemergence (soil-residual) herbicide treatments and 2) Postemergence herbicide treatments. Treatments in the preemergence factor level included a no preemergence herbicide, pyroxasulfone [eg. Zidua], S-metolachlor + fomesafen + metribuzin [eg. Intimidator], and pyroxasulfone + flumioxazin + chlorimuron [eg. Fierce XLT]. Postemergence treatments included programs of only glufosinate [eg. Liberty], tankmixes of dicamba [eg. Xtendimax] or glufosinate plus glyphosate [eg. Roundup PowerMax], and a planned two pass program of dicamba plus glyphosate followed by glufosinate. The factorial design created sixteen treatments with a combination of every preemergence treatment with every postemergence treatment. This design allowed us to observe the significant impact of preemergence treatments versus postemergence as well as any interactions that occurred. Density counts within each plot were conducted in late July 2019 after all applications had been applied. Due to stewardship guidelines with the Xtend Flex soybean and in an effort to reduce further Amaranthus seed development, these sites were destroyed following density counts. RESULTS: Differences in waterhemp densities in late July were influenced by preemergence herbicides at both Taylor and Caldwell Counties. Taylor County waterhemp densities ranged from 1 to 5 plants per 3m2, with plots receiving no preemergence herbicide resulting in greater densities than plots receiving a preemergence herbicide. Caldwell county waterhemp densities ranged from 5 to 40 plants per 3m2, with the Untreated and Fierce XLT plots having similar densities that were greater than the Zidua and Intimidator treatments). While it would be expected that untreated or no preemergence treatments would have greater densities than the Zidua and Intimidator plots, the similarity to the Fierce XLT treatment is unexpected. Though further analysis of early season crop injury ratings revealed that residual injury did occur consistently at this site in plots receiving Fierce XLT with symptoms indicative of chlorimuron injury. The delay in development in these plots likely allowed late season waterhemp flushes to occur as compared to the other preemergence plots where crop injury did not occur. The combination of maximum application rate and cool saturated soil conditions likely led to the injury that occurred to the soybean plots treated with Fierce XLT. At both Caldwell and Taylor county the use of a preemergence herbicide showed reductions of waterhemp densities at the end of the season as compared to plots not receiving a preemergence herbicide. Palmer amaranth densities at Fulton county raged from 1 to 6 plants per 3m2 when analyzing the influence of preemergence herbicides. Intimidator with three effective sites of action resulted in lower Palmer amaranth densities than treatment not receiving a preemergence herbicide application. Differences in either waterhemp or Palmer amaranth densities due to postemergence herbicide applications only occurred at the Taylor county site. The Xtendimax plus Roundup Powermax treatment resulted in greater waterhemp densities than all other postemergence treatments at the site. This difference likely occurred due to only one postemergence application occurring due to growth stage restrictions as compared to the other treatments in which a second postemergence application was applied. CONCLUSIONS: The pending introduction of Roundup Ready 2 XtendFlex soybean will bring a versatile herbicide resistance trait package to Kentucky farmers that allows flexibility of postemergence herbicide applications. The flexibility to apply either dicamba (Xtendimax) or glufosinate (Liberty) allows for options for waterhemp and Palmer amaranth in an environment that may restrict the use of dicamba due to off-target movement concerns. Despite the overall effectiveness of both dicamba and glufosinate in combination with glyphosate, the sole reliance on just postemergence herbicides is likely to lead to further herbicide resistance. In addition, this research has further proven that a robust preemergence herbicide with multiple sites of action reduces end of season Amaranthus densities in comparison to not using a preemergence herbicide.