The last decade has witnessed a steady embrace of genomic and personalized medicine by senior government officials, industry leadership, health care providers, and the public. Genomic medicine, which is the use of information from genomes and their derivatives (RNA, proteins, and metabolites) to guide medical decision making-is a key component of personalized medicine, which is a rapidly advancing field of health care that is informed by each person's unique clinical, genetic, genomic, and environmental information. As medicine begins to embrace genomic tools that enable more precise prediction and treatment disease, which include "whole genome" interrogation of sequence variation, transcription, proteins, and metabolites, the fundamentals of genomic and personalized medicine will require the development, standardization, and integration of several important tools into health systems and clinical workflows. These tools include health risk assessment, family health history, and clinical decision support for complex risk and predictive information. Together with genomic information, these tools will enable a paradigm shift to a comprehensive approach that will identify individual risks and guide clinical management and decision making, all of which form the basis for a more informed and effective approach to patient care. DNA-based risk assessment for common complex disease, molecular signatures for cancer diagnosis and prognosis, and genome-guided therapy and dose selection are just among the few important examples for which genome information has already enabled personalized health care along the continuum from health to disease. In addition, information from individual genomes, which is a fast-moving area of technological development, is spawning a social and information revolution among consumers that will undoubtedly affect health care decision making. Although these and other scientific findings are making their way from the genome to the clinic, the full application of genomic and personalized medicine in health care will require dramatic changes in regulatory and reimbursement policies as well as legislative protections for privacy for system-wide adoption. Thus, there are challenges from both a scientific and a policy perspective to personalized health care; however, they will be confronted and solved with the certainty that the science behind genomic medicine is sound and the practice of medicine that it informs is evidence based.