he Human Genome Project’s generation of a reference human genome sequence was a landmark scientific achievement of historic significance. It also signified a critical transition for the field of genomics, as the new foundation of genomic knowledge started to be used in powerful ways by researchers and clinicians to tackle increasingly complex problems in biomedicine. To exploit the opportunities provided by the human genome sequence and to ensure the productive growth of genomics as one of the most vital biomedical disciplines of the 21st century, the National Human Genome Research Institute (NHGRI) is pursuing a broad vision for genomics research beyond the Human Genome Project. This vision includes using genomic data, technologies, and insights to acquire a deeper understanding of genome function and biology as well as to uncover the genetic basis of human disease. Some of the most profound advances are being catalyzed by revolutionary new DNA sequencing technologies; these methods are producing prodigious amounts of DNA sequence data as part of studies aiming to elucidate the complexities of genome function and to unravel the genetic basis of rare and complex diseases. Together, these developments are ushering in the era of genomic medicine.