Organophosphate (OP) pesticides are the most common source of human toxicity globally, causing high mortality and morbidity despite the availability of atropine as a specific antidote and oximes to reactivate acetylcholinesterase. The primary toxicity mechanism is inhibition of acetylcholinesterase (AchE), resulting in accumulation of the neurotransmitter, acetylcholine, and abnormal stimulation of acetylcholine receptors. Thus, the symptoms (muscarinic, nicotinic, and central nervous system) result from cholinergic overactivity because of AchE inhibition. OP can also cause rhabdomyolysis, pancreatitis, parotitis, and hepatitis. OP therapy includes decontamination, supportive therapy, and the use of specific antidotes such as atropine and oximes. However, there has been a paucity of controlled trials in humans. Here we evaluated the literature for advances in therapeutic strategies for acute OP poisoning over the last 10 years.