Background　With the aging of our society and the improvement of medical technology, the population of elderly patients subjected to surgery is increasing. As these patients are vulnerable to postoperative delirium (POD), cautions should be taken during operations. The prevention of POD is still difficult because the pathophysiological mechanisms underlying POD remains unclear.　Objective　To review the pathophysiology of POD and provide new insights for neural circuit mechanisms underlying POD.　Content　POD results from dysfunction of the central nervous system following operation. Its diagnosis relies on reduction of brain waves, and patients' performance in confusion assessment method. These functional abnormalities may be based on pathophysiological traits observed in POD patients, including altered neurotransmitter release, elevated permeability in blood-brain barrier, exacerbated neuron aging, dysregulated neuroendocrine system, disrupted sleep-wake cycles, and destructed neural network.　Trend　POD might be initiated from the alteration of the monoamine neurotransmitter system, whose vulnerability may associated with the polymorphism of genes in this system. Further investigations are warranted to address the specific neural network immediately related to the outcomes of POD so that the target-directed treatment can be achieved.