A challenge to the realization of the vision of personalized medicine is our lack of under-standing of the amount of genetic variation contained in the human species, which has been prohibitively expensive to acquire to date. In this review, we discuss a new sys-tem based on massively parallel picotiter plate based sequencing. This approach, now commercially available, delivers in excess of 200,000 individual clonal reads in a single five hour run and hence provides orders of magnitude improvement in speed and cost over conventional Sanger-based sequencing. The system is scalable well beyond its cur-rent performance and its emergence makes plausible the routine sequencing of individual human genomes in the near future. In this review, our system is presented in light of recent NHGRI sequencing technology grants, and a number of new applications enabled by ready access to hundreds of thousands of individual clonal reads are discussed with a particular focus on their potential impact on human health.