The Vienna protocol for [153]Sm-EDTMP-therapy is based on the experience of the last two decades. Repeated treatments at a low dose are applied by several authors in order to achieve the maximum therapeutic effect with the lowest haematological toxicity. Significant benefits on pain palliation and some regression are documented. In contrast to earlier claims, [153]Sm-EDTMP treatment should be started as soon as more than 1 bone lesion appears in bone scintigraphy and/or bone pain becomes evident. Prospective randomized controlled studies, however, are urgently warranted in order to assess benefits beyond bone pain palliation on an evidence base. The combination with chemotherapy as well as radiotherapy may further improve the clinical results. Further research should be directed to identify underlying mechanisms of response and predictors of benefit and to elaborate an improved therapeutic schedule for further enhancing the response rate.