Abstract: Glyphosate, a broad-spectrum herbicide targeting 5-enolpyruvylshikimate-3-phosphate synthase, was first commercialized in 1974. Its use increased significantly following the introduction of glyphosate-resistant (GR) crops in 1996 and the expiration of its patent in 2000, making it the most used herbicide worldwide. Intensive reliance on glyphosate has selected for GR weed populations, with the first documented case reported also in 1996. Glyphosate resistance now has evolved in 62 weed species across 31 countries, often involving multiple other herbicide modes of action and thereby complicating chemical control. The highest incidence has occurred in regions with extensive GR crop cultivation, particularly the United States, Brazil, and Argentina, where glyphosate has been used for years as the sole or major herbicide. Apparent disparities among countries largely reflect differences in the timing and reporting of first unique resistance cases, rather than actual differences in the overall prevalence of GR weeds. GR weeds possess the greatest diversity of resistance mechanisms described for any herbicide, encompassing both target-site and non-target-site resistance mechanisms, frequently in combination. In many cases, resistance traits that provide low resistance levels have combined over time to provide more robust resistance (creeping resistance). Evolution and spread of glyphosate resistance are influenced by frequency of use, herbicide dose, phenological stage, pollination biology, gene flow, and dissemination of GR seeds or propagules via contaminated seed/grain lots and machinery. Glyphosate resistance and controversies regarding environmental and health issues have so far not resulted in marked reductions in glyphosate use nor in the introduction of a herbicide or other technology that is as effective and economical as glyphosate in managing weeds. This review synthesizes current knowledge of glyphosate resistance and its mechanisms, highlighting existing gaps, and discusses potential scenarios for the future of glyphosate and GR crops. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.