Genome and exome analyses have become instrumental in establishing genetic diagnoses for critically ill newborns and in cases of previous diagnostic dilemmas. Genome and exome sequencing of presumably healthy individuals is now gaining traction. The roll-out of genomic medicine to the generally healthy population offers a new opportunity to provide insights into the current and future healthcare of individuals and their families. Indeed, numerous projects such as Geisinger’s MyCode Initiative, the National Human Genome Research Institute (NHGRI)’s ClinSeq, and the various Genomes2People research projects at Brigham Health and Harvard Medical School are investigating the use of genome sequencing for apparently healthy individuals. However, there are many scientific and ethical questions about the benefits, harms, and costs of this approach. Here, we explore the opportunities and challenges of utilizing genomic data for predictive, precision, and personalized medicine with several experts in the field.