Auger-emitting radionuclides have potential for the therapy of cancer due to their high level of cytotoxicity and short-range biological effectiveness. Biological effects are critically dependent on the sub-cellular (and sub-nuclear) localization of Auger emitters. Mathematical modelling studies suggest that there are theoretical advantages in the use of radionuclides with short half-lives (such as 123I) in preference to those (such as 125I) with long half-lives. In addition, heterogeneity of radionuclide uptake is predicted to be a serious limitation on the ultimate therapeutic effect of targeted Auger therapy. Possible methods of targeting include the use of analogues of DNA precursors such as iodo-deoxyuridine and molecules which bind DNA such as steroid hormones or growth factors. A longer term possibility may be the use of molecules such as oligonucleotides which can discriminate at the level of DNA sequence. It seems likely that the optimal clinical role of targeted Auger therapy will be as one component of a multi-modality therapeutic strategy for the treatment of selected malignant diseases.