Background: Poisoning by Organophosphorus compounds (OPs) still is a major therapeutic problem. Intentional OPs insecticide poisoning results in up to 300.000 deaths each year and highly toxic OPs nerve agents pose a permanent threat for the civilian population and military forces. The therapeutic value of clinically used oximes, pralidoxime, obidoxime and TMB-4, in human OPs insecticide poisoning is under debate. Moreover, these oximes lack efficacy in poisoning by various nerve agents. An innumerable number of novel oximes have been synthesized in the past five decades to provide more effective oximes and compounds with improved blood–brain-barrier penetration. Novel compounds were tested with largely different experimental protocols in vitro and in animals in vivo. The lack of comparable experimental conditions and the absence of human in vivo studies hamper a well-founded evaluation of the available data.