The target organ for anaesthetic drugs is the brain. For many years, it has been assumed that their effects do not outlast their pharmacological action, that the target organ is restored to its previous state once the agent is eliminated. There is increasing evidence that this is not true, that long term or even permanent neuronal and neurological change can follow administration of anaesthetic drugs. The brain appears to be particularly vulnerable at the beginning and end of its life. Animal studies have suggested that permanent changes may be induced in developing brains, 12 23 but this review will concentrate on changes which may occur in the ageing brain. The earliest manifestation of neuronal damage in the brain is a decline in the higher cortical functions of storage and recall of memory and cognitive processing. The increasingly aged population has stimulated research into premature cognitive decline from all causes. A number of studies have investigated postoperative cognitive dysfunction (POCD), predominantly in the elderly, and these will be discussed together with theories on causation and the limited animal work available thus far. One of the difficulties of human research in this area is that anaesthesia is hardly ever administered as a sole procedure but is almost invariably given to facilitate surgery. As will be discussed below, the stress response to surgery has been suggested as a possible mechanism for POCD. Thus, in all human studies, the term ‘operation’ should be understood to include both anaesthesia and surgery.