The fourth Personal Genomes meeting was held at Cold Spring Harbor Laboratory, New York, from 30 September to 2 October and provided an exciting collection of science built on recent significant milestones in individual human genome sequencing, from the first personal genomes to thousands of human genomes sequenced. As ultra-high throughput sequencing platforms enable the production of more and more individual genomes, a growing number of scientists, physicians, and clinical geneticists are actively exploring the promise and the implications of these new data. Personal Genomes brought many of these pioneers together with nearly 200 scientists, physicians, ethicists, and others to discuss the progress and opportunities around the sequencing and medical interpretation of individual genome sequences. Hum Mutat 33:1016–1019, 2012. © 2012 Wiley Periodicals, Inc.