Radiolabeled monoclonal antibodies and their F(ab')2 and Fab fragments have been successful for imaging and therapy. However, their prolonged circulation and nonspecific accumulation in metabolic organs have resulted in high background radioactive levels and delayed imaging times. Current approaches are two- and three-step procedures consisting of first, the injection of a targeting moiety, which has specific binding affinity for both a lesion and a small molecular weight radiolabeled agent, and, second, a subsequently injected radioactive diagnostic or therapeutic agent. The rapid blood clearance of the free radiolabeled agent greatly reduces background levels and radiation dose and increases target-to-background ratios. This review will focus on two different approaches: 1) bispecific monoclonal antibodies and 2) monoclonal antibodies in conjunction with the streptavidin (avidin)/biotin system.