Now that radioimmunotherapy is an approved method for the treatment of certain types of non-Hodgkin's lymphoma, investigators are turning to new approaches to further improve radionuclide targeting in hopes of expanding the use of this technology. A number of innovative recombinant proteins have been developed with more favorable pharmacokinetic and targeting properties than standard whole IgG, which conceivably could improve the therapeutic index for cancer treatment. Pretargeting methods also are coming of age, with preclinical and early clinical studies in a variety of cancers illustrating how this alternative approach can enhance the therapeutic window several-fold of what has been possible with directly radiolabeled IgG. This review will discuss some of these promising new developments.