Safety and economics of uranium utilization for nuclear power generation were investigated and discussed. In order to sustain energy supply with nuclear power generation, uranium resources should be abundant. From the viewpoint of depletion of the resources, fast breeder reactor (FBR), which is breeder reactor of plutonium, has been developed. In this context, the uranium utilization and plutonium utilization with breeding by FBR are compared and discussed from the viewpoint of safety, sustainability, and energy security. In addition, the significance of partitioning and transmutation (P&T), which is one of the advantages of FBR, was also discussed from the viewpoint of environmental burden from radioactive waste.