Rapid advances in genome sequencing technology are enabling increasingly detailed analysis of human genetic variation. In the next year, we expect to analyze >50,000 deeply sequenced human genomes, corresponding to ~10 million billion bases of raw sequence data. The generation, transfer and analysis of the data presents many opportunities for scientific discovery - enabling better understanding of human history, biology and disease. It also presents varied computational and analytical challenges as well as opportunities to develop and implement new analytical strategies and modes of data sharing. I will illustrate these challenges and opportunities with examples from his ongoing studies.