Acute organophosphate insecticide poisoning can manifest 3 different phases of toxic effects, namely, acute cholinergic crisis, intermediate syndrome (IMS), and delayed neuropathy. Among them, IMS has been considered as a major contributing factor of organophosphate-related morbidity and mortality because of its frequent occurrence and probable consequence of respiratory failure. Despite a high incidence, the pathophysiology that underlies IMS remains unclear. Previously proposed mechanisms of IMS include different susceptibility of various cholinergic receptors, muscle necrosis, prolonged acetylcholinesterase inhibition, inadequate oxime therapy, downregulation or desensitization of postsynaptic acetylcholine receptors, failure of postsynaptic acetylcholine release, and oxidative stress-related myopathy. The clinical manifestations of IMS typically occur within 24 to 96 hours, affecting conscious patients without cholinergic signs, and involve the muscles of respiration, proximal limb muscles, neck flexors, and muscles innervated by motor cranial nerves. With appropriate therapy that commonly includes artificial respiration, complete recovery develops 5–18 days later. Patients with atypical manifestations of IMS, especially a relapse or a continuum of acute cholinergic crisis, however, were frequently reported in clinical studies of IMS. The treatment of IMS is mainly supportive. Nevertheless, because IMS generally concurs with severe organophosphate toxicity and persistent inhibition of acetylcholinesterase, early aggressive decontamination, appropriate antidotal therapy, and prompt institution of ventilatory support should be helpful in ameliorating the magnitude and/or the incidence of IMS. Although IMS is well recognized as a disorder of neuromuscular junctions, its exact etiology, incidence, and risk factors are not clearly defined because existing studies are largely small-scale case series and do not employ a consistent and rigorous definition of IMS. Without a clear understanding of the pathophysiology of IMS, specific therapy is not available. The prognosis of IMS, however, is likely to be favorable if respiratory failure can be promptly recognized and treated accordingly.