The production of biomaterials with the capacity to bind tightly and specifically to cell surface receptors of malignant cells can greatly benefit cancer diagnosis and treatment. Whereas antibodies have the ability to specifically recognize some tumor cell makers, their large size and immunogenecity markedly limit their value. The development of nuclease-resistant oligonucleotide agents, termed aptamers, offers an alternative to antibodies as targeting, diagnostic, and delivery agents. Using the systematic evolution of ligands by exponential enrichment (SELEX) methodology or other variations, one can select specific sequences that have appropriate binding affinities and specificities against clinically relevant markers from large libraries of oligonucleotide ligands. Aptamers have been found to bind their targets with high specificity and with dissociation constants in the subnanomolar or picomolar range. However, the possibility for the selected aptamers to be developed as targeting agents for diagnostic imaging or targeted radiotherapy purposes has yet to be realized. Peptide-coupling reactions between amino and carboxylic groups offer the possibility of labeling the aptamers with a number of chelators that, coupled with appropriate radionuclides, would generate novel targeted radiopharmaceuticals for the diagnosis and therapy of disease. The unparalleled combinatorial chemical diversity, small size, and modification ability of aptamers is expected to meet the criteria for robust, generic drug discovery technology and open new horizons for the development of future radiopharmaceuticals.