Postoperative cognitive dysfunction (POCD) describes a decline in cognitive function for weeks or months after surgery with a prevalence in the elderly patient. Numerous methodological limitations make the interpretation of this clinical syndrome, based on the available literature on POCD, difficult, particularly the different definitions of POCD, the lack of control groups and the relative inconsistency in the occurrence of memory deficits. Several theories have been advanced to explain these observations, but although there is general agreement that POCD is likely to be multifactorial, whether its occurrence is a result of the effects of surgery or general anesthesia remains unclear. This review provides a synopsis of the available clinical and preclinical data and summarizes recent research relevant to the occurrence of POCD and possible pharmacologic algorithms for its prevention and treatment. The effects of volatile and intravenous anesthetics on synaptic transmission and synaptic plasticity, which might be related to cognitive dysfunction in the postoperative period, will be discussed. Unraveling these mechanisms should provide helpful indices for the identification, synthesis and development of new chemical entities suitable for therapeutic use.