Advances in human genetics have begun to yield clinical benefits through the development of Precision Medicine (PM). The benefits of this innovation are promising, both through application of constitutional genetics detecting mutations that affect the risk of disease and tumor genetics, and malignancy-causing mutations susceptible to targeted therapies. While PM may ultimately be used in all aspects of medicine, to date, the most fruitful applications have been in maternal-fetal medicine and cancer. However, due to the complexity and cost of developing these innovations, and to privacy issues, advancing PM is a challenge in traditional clinical, reimbursement, and regulatory landscapes. Although much of the literature focuses on challenges in relating constellations of mutations to the identification of actual current or potential disease states, and to the efficacy of treatments, diffusion of PM also depends on many non-clinical factors. For example, how will information on accurate diagnosis and treatment success be disseminated, and who will bear the cost? How might physician training change to incorporate genetic, probability, statistics, and economic considerations? How can patients reconcile with the ethical and privacy concerns related to the availability of genetic information? Will the era of PM yield still more disparities in access to care? Will cost-effectiveness analysis need to change to better take into account patient heterogeneity? This volume explores the intersection of the scientific, clinical, and economic factors to consider in developing PM. We explore the theoretical and historical underpinnings of PM, discuss implementation issues, and present examples of real-world applications.