Until about 50 years ago, the altering of a normal drug effect by a genetic deficiency was only rarely observed. Here, my discovery of the genetic variant of butyrylcholinesterase affecting succinylcholine action is described in some detail. Such discoveries led to the combination of the two older sciences, genetics and pharmacology, thereby forming pharmacogenetics. After the discovery of similar examples in the years that followed, pharmacogenetics expanded on the basis of two discoveries. First, the common occurrence of interethnic differences in drug response and, secondly, the fact that most pharmacological differences were multigenic. New methodologies brought a transition to pharmacogenomics; this included detection of clinically important genetic variants and has uncovered potentially new drug targets. The arrival of personalised medicine--where a patient's genes determine the choice of drug to be administered--can be hoped to gradually improve drug safety and efficacy. Efforts to reach this level of perfection are, however, dogged by uncertainties.