Postoperative cognitive dysfunction (POCD) is a cognitive impairment syndrome of multifactorial etiology after general anesthesia and surgery. The urgency of the problem associated with the prevention and correction of POCD is due to its high frequency particularly in elderly patients and to the long-term sequels that impair quality of life. To date, the possibilities of preventing POC remain controversial; there is no generally accepted effective strategy for reducing its incidence. A number of proposed techniques aimed at reducing the risk of cognitive impairments lead, among other things, to improvements in surgical and anesthetic techniques with transition to minimally invasive interventions and to the use of short-acting general anesthetics. However, by taking into account the multifactorial genesis of POCD and the involvement of mechanisms, such as neuroinflammation and apoptosis, in its development, the additional use of neuroprotective agents seems justified. Further investigations are needed to develop effective therapeutic strategies for treating POCD. This review gives the data currently available in the literature on the clinical phenomenology, pathogenesis, treatment, and pharmacological prevention of POCD.