Non-invasive, quantitative and repetitive imaging of biological processes in living animals is rapidly changing the way in which many experiments in models of human disease and normal physiological processes are conducted. This review summarizes the newest molecular imaging approaches to analyzing reporter gene expression, with particular emphasis on pre-clinical cancer research. Alternative modes of imaging are summarized, followed by descriptions of the major reporter gene systems now used for radionuclide imaging in vivo of gene expression. Several somatic delivery paradigms for co-ordinate expression of therapeutic and imaging genes are presented, and our own emphasis on the dopamine D2 receptor and Herpes Simplex Virus Type I thymidine kinase reporter genes are detailed.