This chapter focuses on key issues on high-level radioactive wastes (HLW) isolation. HLWs include both spent nuclear fuel and various highly radioactive materials such as transuranic (TRU) radionuclides obtained in the reprocessing of spent nuclear fuel. Transuranic wastes, which are solid radioactive elements obtained from the irradiation of uranium and thorium in the reactors, contain isotopes that have atomic numbers higher than uranium. In anticipation of permanent safe and secure long-term isolation-disposal of HLW in the form of spent nuclear fuel, most operators of nuclear power plants have opted to adopt a two-step holding procedure. The first step entails cooling of the spent fuel material in cooling ponds for a period ranging from 5 to 10 years. The second step following cooling of the spent fuel would be to contain them in dry storage casks made with proper shielding that includes steel and concrete components.