Genetically modified (GM) crops have been and continue to be a subject of controversy despite their rapid adoption by farmers where approved. For the last two decades, an important matter of debate has been their impact on pesticide use, particularly for herbicide-tolerant (HT) crops. Some claim that these crops bring about a decrease in herbicide use, while others claim the opposite. In fact, since 1996, most cultivated GMOs have been GMHT crops, which involve the use of an associated herbicide, generally glyphosate. In their very first years of adoption, HT crops often led to some decrease in herbicide use. However, the repetition of glyphosate-tolerant crops and of glyphosate only applications in the same fields without sufficient alternation and herbicide diversity has contributed to the appearance of glyphosate-resistant weeds. These weeds have resulted in a rise in the use of glyphosate and other herbicides. This article explores this situation and the impacts of herbicide-resistant weeds, using an interdisciplinary approach and drawing on recent data. The paper analyzes the spread of GMHT crops worldwide and their consequences on herbicide use in the USA in particular. It then addresses the global development of glyphosate-resistant weeds and their impact, particularly focusing on the USA. Finally, the last section explores how industry, farmers, and weed scientists are coping with the spread of resistant weeds. The concluding comments deal more widely with trends in GM crops.