Organophosphorus pesticide self-poisoning is a major clinical and public health problem in rural Asia, killing an estimated 200,000 people annually. It is a significant cause of death from self-harm, with about 60% of such deaths attributed to pesticide poisoning. The case fatality rate is generally over 15%, and medical management remains challenging. The core treatments—atropine, oximes, and diazepam—remain unclear in optimal use. Early resuscitation with atropine, oxygen, respiratory support, and fluids is crucial. Oximes may benefit only specific patients or those with moderate poisoning. New treatments like magnesium sulphate show potential, but larger trials are needed. Gastric lavage should be reserved for stable patients. Randomized controlled trials are ongoing in rural Asia to assess these therapies. Bans on highly toxic pesticides could reduce case fatality. Improved medical management and antidote availability could reduce deaths from self-harm in rural Asia. Cholinesterase assays are used for diagnosis but have limitations. Butyrylcholinesterase assays are not reliable for clinical severity, while red-cell acetylcholinesterase assays are better markers of poisoning severity. Oximes may be ineffective for certain pesticides, and their use is not well established. Atropine remains the mainstay of treatment, but its use is not fully optimized. Other muscarinic antagonists like glycopyrronium and hyoscine have different CNS penetration and effectiveness. Oximes are effective in some cases but not all. Benzodiazepines are used for agitation, and magnesium sulphate may reduce mortality in some cases. Gastric lavage is not effective and should be avoided. Activated charcoal and other decontamination methods have limited benefit. New therapies like recombinant bacterial phosphotriesterases may offer future solutions. Overall, further research is needed to optimize treatment and reduce deaths from organophosphorus pesticide poisoning.Organophosphorus pesticide self-poisoning is a major clinical and public health problem in rural Asia, killing an estimated 200,000 people annually. It is a significant cause of death from self-harm, with about 60% of such deaths attributed to pesticide poisoning. The case fatality rate is generally over 15%, and medical management remains challenging. The core treatments—atropine, oximes, and diazepam—remain unclear in optimal use. Early resuscitation with atropine, oxygen, respiratory support, and fluids is crucial. Oximes may benefit only specific patients or those with moderate poisoning. New treatments like magnesium sulphate show potential, but larger trials are needed. Gastric lavage should be reserved for stable patients. Randomized controlled trials are ongoing in rural Asia to assess these therapies. Bans on highly toxic pesticides could reduce case fatality. Improved medical management and antidote availability could reduce deaths from self-harm in rural Asia. Cholinesterase assays are used for diagnosis but have limitations. Butyrylcholinesterase assays are not reliable for clinical severity, while red-cell acetylcholinesterase assays are better markers of poisoning severity. Oximes may be ineffective for certain pesticides, and their use is not well established. Atropine remains the mainstay of treatment, but its use is not fully optimized. Other muscarinic antagonists like glycopyrronium and hyoscine have different CNS penetration and effectiveness. Oximes are effective in some cases but not all. Benzodiazepines are used for agitation, and magnesium sulphate may reduce mortality in some cases. Gastric lavage is not effective and should be avoided. Activated charcoal and other decontamination methods have limited benefit. New therapies like recombinant bacterial phosphotriesterases may offer future solutions. Overall, further research is needed to optimize treatment and reduce deaths from organophosphorus pesticide poisoning.