Organophosphorus pesticide self-poisoning is a significant clinical and public health issue in rural regions of the developing world, causing an estimated 200,000 deaths annually. Medical management is challenging, with a case fatality rate generally exceeding 15%. The core treatments—atropine, oximes, and diazepam—are not well understood, and there is limited evidence to guide therapy. Key factors include early resuscitation with atropine, oxygen, respiratory support, and fluids, as well as the role of oximes, which may benefit only patients poisoned by specific pesticides or with moderate poisoning. New treatments like magnesium sulfate show promise but require larger trials. Gastric lavage can be beneficial but should be performed only after the patient is stable. Randomized controlled trials are underway in rural Asia to assess these therapies. However, some organophosphorus pesticides may be difficult to treat with current methods, suggesting that bans on certain pesticides could be necessary to significantly reduce case fatality. Improved medical management and provision of antidotes and intensive care beds, along with bans on highly toxic pesticides, should reduce the case fatality rate and deaths from self-harm in rural Asia.Organophosphorus pesticide self-poisoning is a significant clinical and public health issue in rural regions of the developing world, causing an estimated 200,000 deaths annually. Medical management is challenging, with a case fatality rate generally exceeding 15%. The core treatments—atropine, oximes, and diazepam—are not well understood, and there is limited evidence to guide therapy. Key factors include early resuscitation with atropine, oxygen, respiratory support, and fluids, as well as the role of oximes, which may benefit only patients poisoned by specific pesticides or with moderate poisoning. New treatments like magnesium sulfate show promise but require larger trials. Gastric lavage can be beneficial but should be performed only after the patient is stable. Randomized controlled trials are underway in rural Asia to assess these therapies. However, some organophosphorus pesticides may be difficult to treat with current methods, suggesting that bans on certain pesticides could be necessary to significantly reduce case fatality. Improved medical management and provision of antidotes and intensive care beds, along with bans on highly toxic pesticides, should reduce the case fatality rate and deaths from self-harm in rural Asia.