Noninvasive imaging systems include a wide range of technologies that make use of different contrast mechanisms to provide images that can reflect anatomy, physiology, metabolism, and more specifically interactions with proteins, gene expression, or to track therapeutic molecules and transplanted stem and progenitor cells. While in vivo imaging technologies are clearly essential for the development of new stem cell therapies for humans, imaging techniques with sufficient sensitivity to detect small quantities of cells are needed to monitor and evaluate safety and efficiency of new stem cell therapies for a spectrum of human diseases. Nuclear medicine techniques, especially positron emission tomography (PET), have much higher sensitivity than other imaging modalities and can provide 3D quantitative images. Outcomes using PET imaging can also be translated from animal models to humans. These studies focused on two overriding objectives: to assess current PET imaging systems with the goal of understanding and improving detection and quantification of stem cells transplanted in vivo; and to develop methods to radiolabel stem and progenitor cells for transplant and short-term tracking in vivo with PET. These studies have shown that some commercial PET scanners are not as sensitive as others for imaging low-activity sources produced by labeled cells because of inherent background noise that confounds PET imaging. In addition, new methods for labeling cells in vitro and in vivo have been developed that will aid in identifying engrafted stem/progenitor cells using PET post-transplantation.