Yttrium-90 ((90)Y, T(1/2) 64.14 h) is a key example of a high beta energy-emitting radionuclide which is available from the strontium-90 ((90)Sr)/(90)Y radionuclide generator system. Clinical uses of (90)Y-labeled radiopharmaceutical agents have been pursued for many years and many applications have proven to be clinical effective. These most notably include the application of 90Y-labeled antibodies for a variety of applications such as for effective treatment of non-Hodgkin's lymphoma. One of the major advantages for use of (90)Y is ready availability from the very long-lived (90)Sr parent (T(1/2) 28.78 y). Because of the importance of maintaining generator performance and minimizing parent breakthrough, this paper describes development, use and quality control of both high capacity cation adsorption-type and electrochemical generator systems. In addition, the preparation and targeting to tumors in mice of DOTA-conjugated Nimotuzamab (h-R3) antibody which recognizes the external domain of the EPFR antibody radiolabeled with (90)Y obtained from the electrochemical generator is also described. As a key example for clinical applications of (90)Y, the use of (90)Y-labeled biotin for intra-operative pre-targeting for radionuclide therapy (IART®) of breast cancer is also described.