Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of biomedical research. These tools have been validated recently in variety of research models, and have been shown to provide continuous quantitative monitoring of the location(s), magnitude, and time-variation of gene delivery and/or expression. This article reviews the use of PET technologies as they have been used in imaging biological processes for molecular imaging applications. The studies published to date demonstrate that noninvasive imaging tools will help to accelerate pre-clinical model validation as well as allow for clinical monitoring of human diseases. (Nucl Med Mol Imaging 2006;40(6):279-292)