Almost 450 nuclear power plants are currently operating throughout the world and supplying about 17% of the world’s electricity. These plants perform safely, reliably, and have no free-release of byproducts to the environment. Given the current rate of growth in electricity demand and the ever growing concerns for the environment, nuclear power can only satisfy the need for electricity and other energy-intensive products if it can demonstrate (1) enhanced safety and system reliability, (2) minimal environmental impact via sustainable system designs, and (3) competitive economics. The U.S. Department of Energy with the international community has begun research on the next generation of nuclear energy systems that can be made available to the market by 2030 or earlier, and that can offer significant advances toward these challenging goals; in particular, six candidate reactor system designs have been identified. These future nuclear power systems will require advances in materials, reactor physics, as well as thermal-hydraulics to realize their full potential. However, all of these designs must demonstrate enhanced safety above and beyond current light water reactor systems if the next generation of nuclear power plants is to grow in number far beyond the current population. This paper reviews the advanced Generation-IV reactor systems and the key safety phenomena that must be considered to guarantee that enhanced safety can be assured in future nuclear reactor systems.