Although the general radiobiological principles underlying external beam therapy and radionuclide therapy are the same, there are significant differences in the radiobiological effects observed in mammalian cells. In external beam therapy and brachytherapy, emissions are composed of photons, whereas in radionuclide therapy, the radiations of interest are particulate. This article will explore the special features that characterise the biological effects consequent to the traversal of charged particles through mammalian cells. In addition, it will highlight what has been learned when these radionuclides and targeting radiopharmaceuticals are used to treat cancers.