Technical Abstract: In the 2009/2010 growing season, Brazil was the second largest world soybean producer, followed by Argentina. Glyphosate-resistant soybeans (GRS) are being cultivated in most of soybean area in South America. Overall, the GRS system is beneficial to the environment when compared to conventional soybean. GRS resulted in a significant shift to no-tillage practices in Brazil and Argentina, but weed resistance may reduce this trend. Probably the highest agricultural risk in adopting GRS in Brazil and South America is related to weed resistance due to use of glyphosate. Weed species in GRS fields have shifted in Brazil to those that can more successfully withstand glyphosate or to those that avoid the time of its application. Four weed species, Euphorbia heterophylla L., Conyza bonariensis (L.) Cronquist, C. canadensis (L.) Cronquist, and Lolium multiflorum Lam., have evolved resistance to glyphosate in GRS in Brazil. Conyza spp. are the most difficult to control. A glyphosate-resistant biotype of Sorghum halepense L. evolved in GRS in Argentina. The following actions are proposed to minimize weed resistance problem: a) rotation of GRS with conventional soybeans in order to rotate herbicide modes of action, b) avoidance of lower than recommended rates c) keeping soil covered with a crop or legume at intercrop intervals, and d) use of a preplant non-selective herbicide plus residuals to eliminate early weed interference with the crop and to minimize escapes from later applications of glyphosate due to natural resistance of older weeds and/or incomplete glyphosate coverage. Unfortunately, all these actions, in some way compromise one for more of the benefits of the GRS cultivation.