Most patients undergoing autologous hematopoietic stem cell transplantation for malignant diseases suffer recurrences of their neoplasms and die due to the inability of conventional high-dose conditioning regimens to eradicate their malignancies. As a result, intensive efforts to develop more effective conditioning regimens are currently under way at many institutions. Encouraging results have been obtained using targeted radiotherapy with radiolabeled antibodies or bone-seeking isotopes as components of novel conditioning regimens for autologous transplantation of patients with lymphomas, multiple myeloma and bone metastases. Results with radiolabeled antibodies targeting epithelial antigens on solid tumors, however, have been less encouraging. This report reviews the status of clinical studies using myeloablative doses of targeted radiotherapy in patients undergoing autologous stem cell transplantation for hematological malignancies or solid tumors.