Two hundred and twenty weed species have evolved resistance to one or more herbicides, and there are now 404 unique cases (species × site of action) of herbicide-resistant weeds globally. ALS inhibitor-resistant weeds account for about a third of all cases (133/404) and are particularly troublesome in rice and cereals. Although 71 weed species have been identified with triazine resistance, their importance has dwindled with the shift towards Roundup Ready® crops in the USA and the reduction of triazine usage in Europe. Forty-three grasses have evolved resistance to ACCase inhibitors, with the most serious cases being Avena spp., Lolium spp., Phalaris spp., Setaria spp. and Alopecurus myosuroides, infesting more than 25 million hectares of cereal production globally. Of the 24 weed species with glyphosate resistance, 16 have been found in Roundup Ready® cropping systems. Although Conyza canadensis is the most widespread glyphosate-resistant weed, Amaranthus palmeri and Amaranthus tuberculartus are the two most economically important glyphosate-resistant weeds because of the area they infest and the fact that these species have evolved resistance to numerous other herbicide sites of action, leaving growers with few herbicidal options for their control. The agricultural chemical industry has not brought any new herbicides with novel sites of action to market in over 30 years, making growers reliant on using existing herbicides in new ways. In addition, tougher registration and environmental regulations on herbicides have resulted in a loss of some herbicides, particularly in Europe. The lack of novel herbicide chemistries being brought to market combined with the rapid increase in multiple resistance in weeds threatens crop production worldwide.