The ability to label tissue-specific antibodies has long been of interest for improving detection and guidance for therapeutic applications. The most studied target for prostate cancer is the prostate-specific membrane antigen, which is upregulated in prostate cancer, hormone-refractive disease, and prostate cancer metastases. Investigations using radioimmunoscintigraphy with the radiolabeled 7E11 antibody capromab pendetide have significantly improved sensitivity for prostate cancer detection compared with standard cross-sectional imaging, based on tissue confirmation of pathologic results. Over the past 5 years, significantly greater image resolution from improved camera technology and the use of co-registration to fuse functional and anatomic (computerized tomography and magnetic resonance imaging) images have dramatically enhanced prostate cancer localization. Outcomes data from several sources have spurred a resurgence in interest in this imaging modality.