Genetics, and more recently genomics, reveal striking conservation in the fundamental signaling pathways that underlie normal and aberrant cell processes. Consequently, various genetic model organisms are now attracting the interest of biomedical scientists who are focused on therapeutic approaches to human disease. There are now several examples of studies in which Drosophila seems likely to facilitate advances in potential therapies, and a recent report has demonstrated the utility of the fly model for understanding and treating human disease. Basic developmental genetic information first obtained in Drosophila was used to design a therapeutic block to oncogenic Notch signaling that was associated with leukemia in mice. The story of Notch signaling in Drosophila demonstrates the potential for standard Drosophila molecular genetics in developing therapeutic strategies that are relevant to human disease.