The lack of evolution of weed resistance to the herbicide glyphosate has been considered from several perspectives. Few plant species are inherently resistant to glyphosate. Furthermore, the long history of extensive use of the herbicide has resulted in no verified instances of weeds evolving resistance under field situations. Unique properties of glyphosate such as its mode of action, metabolism, chemical structure and lack of residual activity in soil may explain this observation. Selection for glyphosate resistance of crops using intense whole plant and cell/tissue culture techniques, including mutagenesis, has had only limited success and is unlikely to be duplicated under normal field conditions. Information obtained in the development of glyphosate-resistant crops suggests that target-site alterations that decrease the herbicidal activity of glyphosate also may lead to reduced survival of a weed. In addition, the complex manipulations that were required for the development of glyphosate-resistant crops are unlikely to be duplicated in nature to evolve glyphosate-resistant weeds.