Rubin is known for his studies of genetics, genomics, and developmental biology in the fruit fly Drosophila. In 1982, he and Allan Spradling developed methods for making transgenic Drosophila, an advance that had a profound effect on research using the fruit fly. His laboratory at Berkeley did pioneering studies using genetic approaches to discover components of signaling pathways acting downstream of tyrosine kinases. He later led the publicly funded effort to sequence the Drosophila genome, collaborating with Celera Genomics to achieve this goal in 2000.