The molecular biology revolution led to an intense focus on the study of interactions between DNA, RNA and protein biosynthesis in order to develop a more comprehensive understanding of the cell. One consequence of this focus was a reduced attention to whole-system physiology, making it difficult to link molecular biology to clinical medicine. Equipped with the tools emerging from the genomics revolution, we are now in a position to link molecular states to physiological ones through the reverse engineering of molecular networks that sense DNA and environmental perturbations and, as a result, drive variations in physiological states associated with disease.