Positron Emission Tomography (PET) is an imaging modality which can determine biochemical and physiological processes in vivo in a quantitative way by using radiopharmaceuticals labeled with positron emitting radionuclides as 11C, 13N, 15O and 18F and by measuring the annihilation radiation using a coincidence technique. This includes also measurement of the pharmacokinetics of labeled drugs and the assessment of the effects of drugs on metabolism. Because only very low amounts of the radiolabeled drug have to be administered, far below toxicity levels, human studies can be carried out even before the drug is entered in Phase I. 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 to study the metabolic consequences of gene expression or gene defects. In the last decade many genetically engineered small animal models 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 to bridge the gap between molecular biology, understanding of pathology and to the design of a new generation of drugs.