AbstractThe aim of this brief review is to draw information from studies of the mechanism of evolved resistance in weeds, together with information from laboratory studies of paraquat tolerance in model plants. Plants having mutations that limit paraquat uptake into cytoplasm, that confer various stress tolerances or that have transgenes that co‐express two or more of the chloroplast Halliwell–Asada cycle enzymes can all exhibit enhanced tolerance to paraquat. However, none of these mechanisms correspond to the high‐level resistances that have evolved naturally in weeds. Most, but not all, of the evidence from studies of paraquat‐resistant biotypes of weeds can reasonably be reconciled with the proposal of a single major gene mechanism that sequesters paraquat away from chloroplasts and into the vacuole. However, the molecular details of this putative mechanism remain ill‐defined. © 2013 Society of Chemical Industry