This chapter traces the history of attempts and achievements in regulating the use of nuclear energy and material, focusing on nuclear non-proliferation and disarmament. Ever since its invention, the nuclear weapon has occupied a special place in the global security order, both militarily and politically, due to its extraordinary destructive power. This picture is further complicated by the fact that nuclear material has both military and civilian uses. Civilian use of nuclear material includes generating electricity through nuclear reactors. Nuclear material also has medical, agricultural, and other peaceful applications, such as its use in the treatment of cancer. The chapter assesses in detail such treaties as the Partial Test Ban Treaty, the Treaty on the Non-Proliferation of Nuclear Weapons, the Comprehensive Nuclear-Test-Ban Treaty, and the Treaty on the Prohibition of Nuclear Weapons. It also looks at the current challenges involving the Democratic People’s Republic of Korea and Iran.