In reviewing the past decade, it is clear that genomics was, and still is, driven by innovative technologies, perhaps more so than any other scientific area in recent memory. From the outset, computing, mathematics and new automated laboratory techniques have been key components in allowing the field to move forward rapidly. We highlight some key innovations that have come together to nurture the explosive growth that makes a new era of genomics a reality. We also document how these new approaches have fueled further innovations and discoveries.