PET cellular proliferation imaging has its roots in a long history of in vitro cellular proliferation studies to characterize cancer and in the understanding of the biology of thymidine incorporation into DNA gained from these studies. PET imaging represents the logical translation of the in vitro work to measure in vivo tumor proliferation. Preclinical studies of [11C]-thymidine and other PET-labeled thymidine analogues set the stage for early clinical studies that provided very promising results. Recent progress in the application of [18F]-FLT, a clinically practical PET thymidine analogue, to patient studies sets the next stage for clinical PET cellular proliferation imaging. Further mechanistic studies of the imaging agents and well-designed clinical trials will be important in moving PET proliferation imaging into what is likely to be a significant role in the care of cancer patients by providing a quantitative measure of tumor response to cytotoxic or cytostatic therapy.