Poisoning by organophosphorus pesticides results from inhibition of acetylcholinesterase. The outcome and optimum treatment depend on properties which differ among individual compounds. Treatment consists of supportive care, especially aimed at respiratory complications, and specific antidotal treatment. Treatment with atropine and diazepam is well established, but there is controversy concerning treatment with oximes capable of forcing reactivation of inhibited acetylcholinesterase. Although all parameters have not been fully established, initial bolus doses followed by continuous intravenous infusion to achieve plasma concentrations of 85–170 μmol/L of pralidoxime or 10–20 μmol/L of obidoxime have been recommended. These are well above concentrations that were likely to have been achieved by many of the ineffective regimens reported in the literature. Several independent reasons for failure of attempts at oxime therapy are discussed in this overview. If nothing else, it is likely that maintenance of adequate levels of oxime will shorten the period that a patient requires assisted ventilation with its associated risks. Topics for further laboratory and clinical research are listed. It is important to seek further understanding and the introduction of better practice because death rates from this type of poisoning remain significant.