Over the last 30 years, the research agenda of Isaac Kohane has been driven by the vision of what biomedical researchers could do to find new cures, provide new diagnoses and deliver the best care available if data could be converted more rapidly to knowledge and knowledge to practice. In so doing, Kohane has designed and led multiple internationally adopted efforts to “instrument” the healthcare enterprise for discovery and to enable innovative decision-making tools to be applied to the point of care. At the same time, the new insights afforded by ’omic-scale molecular analyses have inspired him and his collaborators to work on re-characterizing and reclassifying diseases such as autism, rheumatoid arthritis and cancers. In many of these studies, the developmental trajectories of thousands of genes have been a powerful tool in unraveling complex diseases.