Abstract: Pyruvate dehydrogenase complex (PDHc) is an important herbicide target enzyme. PDHc is a key oxidoreductase in organism and it catalyzes the oxidative decarboxylation of pyruvate to acetyl coenzyme A. Many organophosphorus compounds have been proven to be effective inhibitors of plant PDHc. In this review, the research progress and trend of PDHc inhibitors as herbicides were systematically introduced. Including the research work of our group, the discovery of phosphorous analogues as lead structures of PDHc inhibitors, optimization of lead compounds, and creation and derivatization of clacyfos were summarized and reviewed.