Most of the naturally occurring radionuclides are very long-lived (e.g., 4oK, T1/2 ~ 109 years) and/or represent very heavy elements (e.g., uranium and radium) that are unimportant in metabolic or physiologic processes. Some of the first applications of radioactivity for medical tracer studies in the 1920s and 1930s made use of natural radionuclides; however, because of their generally unfavorable characteristics indicated above, they have found virtually no use in medical diagnosis since that time. The radionuclides used in modern nuclear medicine all are of the manufactured or "artificial" variety. They are made by bombarding nuclei of stable atoms with subnuclear particles (such as neutrons and protons) so as to cause nuclear reactions that convert a stable nucleus into an unstable (radioactive) one. This chapter describes the methods used to produce radionuclides for nuclear medicine as well as some considerations in the labeling of biologically relevant compounds to form radiopharmaceuticals.