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Glyphosate is the world's most important herbicide, with many uses that deliver effective and sustained control of a wide spectrum of unwanted (weedy) plant species. Until recently there were relatively few reports of weedy plant species evolving resistance to glyphosate. Since 1996, the advent and subsequent high adoption of transgenic glyphosate-resistant crops in the Americas has meant unprecedented and often exclusive use of glyphosate for weed control over very large areas. Consequently, in regions of the USA where transgenic glyphosate-resistant crops dominate, there are now evolved glyphosate-resistant populations of the economically damaging weed species Ambrosia artemissifolia L., Ambrosia trifida L., Amaranthus palmeri S Watson, Amaranthus rudis JD Sauer, Amaranthus tuberculatus (Moq) JD Sauer and various Conyza and Lolium spp. Likewise, in areas of transgenic glyphosate-resistant crops in Argentina and Brazil, there are now evolved glyphosate-resistant populations of Sorghum halepense (L.) Pers and Euphorbia heterophylla L. respectively. As transgenic glyphosate-resistant crops will remain very popular with producers, it is anticipated that glyphosate-resistant biotypes of other prominent weed species will evolve over the next few years. Therefore, evolved glyphosate-resistant weeds are a major risk for the continued success of glyphosate and transgenic glyphosate-resistant crops. However, glyphosate-resistant weeds are not yet a problem in many parts of the world, and lessons can be learnt and actions taken to achieve glyphosate sustainability. A major lesson is that maintenance of diversity in weed management systems is crucial for glyphosate to be sustainable. Glyphosate is essential for present and future world food production, and action to secure its sustainability for future generations is a global imperative.