Rat models have been used for many decades to study physiological and pathophysiological mechanisms. Prior to the release of the rat genome and new technologies for targeting gene manipulation, the rat had been the underdog in the genomics era, despite the abundance of physiological data compared to the mouse. The overarching goal of biomedical research is to improve health and advance medical science. Translating human disease gene discovery and validation in the rat, through the use of emerging technologies and integrated tools and databases, is providing power to understand the genetics, environmental influences, and biology of disease. In this review we briefly outline the rat models, bioinformatics tools, and technologies that are changing the landscape of translational research. The strategies used to translate disease traits to genes to function, and, ultimately, to improve human health is discussed. Finally, our perspective on how rat models will continue to positively impact biomedical research is provided.