Weed resistance to herbicides has dramatically increased in the past decade; consequently, research dedicated to understanding the mechanisms of herbicide resistance has also increased. Several symposia in the past decade have addressed various aspects of resistance to herbicides in weeds or crops. Weedy plants acquire resistance to a herbicide by one or more of the following mechanisms: (1) detoxification of the herbicide, (2) preventing the herbicide from reaching the target site, or (3) alteration of the target site. Thus far, the most prevalent mechanism is target-site mutation. Advances in molecular biology techniques, particularly in the area of deoxyribonucleic acid analysis, have provided opportunities for weed science researchers to study the molecular basis for herbicide resistance. Numerous papers presented at weed science or related forums have discussed genetic modifications at the site of action as the most common mechanism conferring resistance. Mutations at the herbicide-binding site result in conformational changes that inhibit herbicide binding. This mechanism underlies resistance to triazines, aryloxyphenoxypropionates, cyclohexanediones, and acetolactate synthase–inhibiting herbicides. Resistance is generally caused by single or multiple mutations at the herbicide-binding site.