Technical Abstract: Herbicides inhibiting protoporphyrinogen oxidase (Protox) have been commercialized for more than 30 years, although their molecular site of action remained unknown until 1989. The patent literature indicates that there are thousands of compounds, representing numerous chemical classes, with this mode of action. The most active Protox inhibitors apparently compete for the substrate-binding site of Protox, mimicking portions of the protoporphyrinogen molecule. Light is required for the development of injury, with symptoms becoming visible within a few hours of application. The relationship between activity in the field and the mechanism of action of these compounds will be discussed. Most Protox-inhibiting herbicides are usually applied postemergence and have broad spectrum weed control. However, more recent commercial Protox inhibitors are extending their use to new crops and to pre-emergence applications. Still, as a herbicide family, their overall impact on the agrochemical market has been limited to a few major crops due to their relatively narrow selectivity. Future use may increase because weeds have not evolved resistance to these herbicides and high levels of crop resistance may be imparted by genetic engineering. Toxicological issues will be addressed, even though these compounds are not considered to be of significant toxicological risk.