NERSC provides production computing to the DOE Office of Science community with over 3000 users working on 300 distinct projects. The NERSC systems include the Cray XT4 system, know as Franklin, which has over 100 Teraflops of peak performance and a sustained application performance of 19 Teraflops. In addition, NERSC provides archival and online storage, cluster computing, and application consulting services. I will highlight some of the science activities performed at NERSC and describe two new strategic directions for the next 10 years. The first significantly expands the support for analysis of large scientific data sets through a combination of hardware, software, and service activities. The second is to re-think high end computing system design from a power-efficiency perspective, which I believe is necessary to reach the target of Exascale computing. I will talk about initial efforts in these two areas, both using an application-driven approach to finding a general solution to these problems.