Tools that enable manipulation or perturbation of gene function in a spatiotemporal manner are critical to define its contribution to normal development and disease. Unfortunately, current inducible expression systems preclude accurate spatiotemporal control of gene expression and involve steroid hormones, antibiotics, heavy metals, or heat shock, which can induce toxicity or pleiotropic effects. What if transgene expression could be rapidly activated and immediately reversed with a switch triggered by light? Here we present the generation and implementation of a new genetically encoded light-dependent expression system in animal cells based on the fast, reversible photoactivation of Phytochrome B (PhyB) from plants. Phytochromes are light activated biological switches that control plant growth and development. In response to red light, PhyB is activated and moves to the nucleus, triggering a cascade of signal transduction events. Under far-red light, it returns to the inactive state, promptly ending signaling. This system, which we have called PhotoGal4, possesses all the elements required for the formation of active phytochromes in animal cells, including genes essential for chromophore formation as well as important motifs required for transcriptional activity. Our hypothesis is that this system will serve as a high-resolution device to sculpt gene expression in Drosophila with agile on-off control and with unprecedented precision and resolution. Finally, we anticipate that this system will have a variety of applications in many areas of biomedical research, from the development of new therapeutic strategies, to the analysis of complex and multi staged biological processes such as embryogenesis, neurodegeneration and cancer.