The primary limitation on the development of new radiotracers for use with positron emission tomography (PET) is the time constraints created by working with radionuclides with the short half-lives inherent to carbon 11 and fluorine 18, the main radionuclides used in PET radiotracer development. In the past decade there have been several developments in the radiosynthetic methods used in PET chemistry, advances that are expected to lead to an increase in the number of radiotracers making the transition from clinical research studies to clinical PET studies. This article reviews developments in PET radiochemistry that will facilitate this process and discusses the application of these basic principles of PET radiotracer development in central nervous system research. Current status of regulatory requirements for the development of new PET radiotracers for imaging studies in humans is reviewed.