As continuous cell proliferation caused by genetic alterations leads to cancer, monitoring abnormal cell proliferation in sporadic tumor models is important in the context of tumor generation, development and response to therapy. Bioluminescence imaging technology, which visualizes the conversion of chemical energy into visible light by luciferase enzymes, is an established method to measure cell numbers in grafted tumors in vivo, but has not been used to monitor cell proliferation per se. To measure cell proliferation noninvasively, transgenic mice have been developed that express the luciferase gene under the control of the E2F1 promoter. When these reporter mice are crossed with genetically defined mouse models of human cancer, the proliferative activity of the tumor cells can be monitored with proportional light production. These technologies support more detailed preclinical trials and could enable other biological pathways to be monitored in living cells.