Positron emission tomography (PET) provides noninvasive in vivo quantitative pharmacokinetic and pharmacodynamic information on novel and established drugs. Because only very low amounts of the (potential) drug have to be administered, far below toxicity levels, human studies can be carried out even before the drug is entered in phase I studies. Such studies can provide cost-effective predictive toxicology data and information on the metabolism and mode of action of drugs. PET is also very useful in the study of the metabolic consequences of gene expression or gene defects. In the last decade, several models using genetically engineered small animals have been developed. The study of these animals with high-resolution small animal PET cameras provides new opportunities in drug development. Especially valuable is the contribution of PET in bridging the gap between molecular biology, basic pathology and the design of a new generation of drugs.