Although the general radiobiologic principles underlying external beam therapy and radionuclide therapy are the same, there are significant differences in the radiobiologic effects observed in mammalian cells. External beam and brachytherapy emissions are composed of photons, whereas radiations of interest in radionuclide therapy are particulate. The special features that characterize the biologic effects consequent to the traversal of charged particles through mammalian cells are explored with respect to DNA lesions and cellular responses. Information about the ways in which these radionuclides are used to treat cancers in experimental models are highlighted.