The concept of 'personalized medicine' in which a knowledge of genetic factors guides prescribing tailored to the individual is popularly considered to be an inevitable consequence of completion of the International Human Genome Project. We should not forget, however, that a personal or family history of one of several uncommon pharmacogenetic conditions has influenced the use of the implicated drug(s) during anaesthesia for the past 50 yr. Although this has been important for those affected, pharmacogenomics heralds the prospect of an individual's genetic profile informing every prescription. Progress has been rapid in some areas, notably cancer chemotherapy where response to treatment can be predicted on the basis of the genetic profile of the tumour cells. The situation is different for most currently available drugs, including those used by anaesthetists, where genetic variability to drug response is presumed to be the result of a complex interaction of multiple factors. We review the nature and investigation of pharmacogenomic variability and contrast the progress made with research into opioid variability with the more limited literature concerning i.v. and inhalation anaesthetics.