Translational genomics aims to improve human health by building on discoveries made through genetics research and applying them in the clinical setting. This progress has been made possible by technological advances in genomics and analytics and by the digital revolution. Such advances should enable the development of prognostic markers, tailored interventions, and the design of prophylactic preventive approaches. We are at the cusp of predicting disease risk for some disorders by means of polygenic risk scores integrated with classical epidemiological risk factors. This should lead to better risk stratification and clinical decision-making. A deeper understanding of the link between genome-wide sequence and association with well-characterized phenotypes will empower the development of biomarkers to aid diagnosis, inform disease progression trajectories, and allow better targeting of treatments to those patients most likely to respond.