The selection of herbicide-resistant weed populations began with the introduction of synthetic herbicides in the late 1940s. For the first 20 years after introduction, there were limited reported cases of herbicide-resistant weeds. This changed in 1968 with the discovery of triazine-resistant common groundsel. Over the next 15 yr, the cases of herbicide-resistant weeds increased, primarily to triazine herbicides. Although triazine resistance was widespread, the resistant biotypes were highly unfit and were easily controlled with specific alternative herbicides. Weed scientists presumed that this would be the case for future herbicide-resistant cases and thus there was not much concern, although the companies affected by triazine resistance were somewhat active in trying to detect and manage resistance. It was not until the late 1980s with the discovery of resistance to Acetyl Co-A carboxylase (ACCase) and acetolactate synthase (ALS) inhibitors that herbicide resistance attracted much more attention, particularly from industry. The rapid evolution of resistance to these classes of herbicides affected many companies, who responded by first establishing working groups to address resistance to specific classes of herbicides, and then by formation of the Herbicide Resistance Action Committee (HRAC). The goal of these groups, in cooperation with academia and governmental agencies, was to act as a forum for the exchange of information on herbicide-resistance selection and to develop guidelines for managing resistance. Despite these efforts, herbicide resistance continued to increase. The introduction of glyphosate-resistant crops in the 1995 provided a brief respite from herbicide resistance, and farmers rapidly adopted this relatively simple and reliable weed management system based on glyphosate. There were many warnings from academia and some companies that the glyphosate-resistant crop system was not sustainable, but this advice was not heeded. The selection of glyphosate resistant weeds dramatically changed weed management and renewed emphasis on herbicide resistance management. To date, the lesson learned from our experience with herbicide resistance is that no herbicide is invulnerable to selecting for resistant biotypes, and that over-reliance on a weed management system based solely on herbicides is not sustainable. Hopefully we have learned that a diverse weed management program that combines multiple methods is the only system that will work for the long term.Nomenclature: Atrazine; glyphosate; imazethapyr; paraquat; simazine; 2,4-D; common groundsel, Senecio vulgaris L.; giant ragweed, Ambrosia trifida L.; goosegrass, Eleusine indica (L.) Gaertn.; horseweed, Conyza canadensis (L.) Cronq.; johnsongrass, Sorghum halepense (L.) Pers.; common lambsquarters, Chenopodium album L.; Palmer amaranth, Amaranthus palmeri S. Wats.; rigid ryegrass, Lolium rigidum Gaudin.; waterhemp, Amaranthus tuberculatus (Moq.) Sauer.; wild carrot, Daucus carota L.