Field studies were conducted in 2006 and 2007 to evaluate strategies for management of four glyphosate-tolerant common lambsquarters populations in glyphosate-resistant soybeans. Treatments consisted of several different preplant herbicide combinations followed by one or two postemergence applications of 0.84 to 3.36 kg ae/ha of glyphosate. Preplant application of a combination of glyphosate, 2,4-D ester and residual herbicides resulted in the most effective control of all populations, and allowed use of a single postemergence glyphosate application at the lowest rate. Late-season control of common lambsquarters ranged from 66 to 95% where no preplant herbicides were applied, 72 to 97% for preplant application of glyphosate and 2,4-D, and 96 to 100% for the combination of glyphosate, 2,4-D, flumioxazin, and cloransulam-methyl. Individual plants survived and produced seed following single postemergence glyphosate applications of 3.36 kg ae/ha, and multiple glyphosate applications totaling 2.5 kg ae/ha. Multiple postemergence treatments were more effective than single postemergence treatments for reduction of common lambsquarters population density and seed production. The progeny of plants that survived high rates of glyphosate in the field were screened for their response to glyphosate in the greenhouse. Progeny from one of three populations exhibited increased glyphosate tolerance from 1 yr of selection pressure.