The relative opacity of mammalian tissue permits the transmission of light from internal biological light sources in small laboratory animals. As such internally expressed bioluminescence can be detected externally revealing spatiotemporal information about tagged biological functions. Enzymes that emit light, photoproteins, have been characterized photoproteins have been used as reporters in a variety of in vitro and ex vivo assays and are now being employed as sources of internal biological light that can be eternally monitored in living animals. Using this approach, spatiotemporal changes in patterns of gene expression, infectious disease and tumor cell growth can be revealed in real time. Monitoring light emissions from internal sources provides a powerful method for cellular and molecular analyses in living animals. This approach is particularly well suited for the evaluation of potential therapeutics including the efficacy of novel DNA-based therapies and vaccines.