The aim of this paper is to focus on our previous experience with the treatment of Group 3 and 4 neuroblastoma patients and on the therapeutic use of [131I]MIBG, to better define the role of this radioactive drug in the treatment of neuroblastoma (NB). Analysis of the studies on Group 3 patients treated with chemotherapy and surgery showed that the progression-free survival (PFS) increased from 45% for patients treated before 1985 to 63% for patients treated in the period of 1985-1989 and to 78% for patients treated after 1989. [131I]MIBG administered in 17 Group 3 patients who did not achieve a radical excision of the primary resulted in 7 partial response (PR) and 5 minor response (MR), with 10 cases of long term survival. Results in Group 4 patients confirmed the good prognosis in the subset of children aged 6-12 months at diagnosis (PFS 86% at 5 years). In patients aged > 12 months at diagnosis intensive induction chemotherapy induced a higher response rate of 69% and PFS was 26% at 5 years. [131I]MIBG administered in advanced stage 4 patients induced a response in 50% of the cases (2 complete response [CR], 13 PR and 2 MR out of 34 children) and 8 children treated for residual primary (4 cases) or residual bone metastases (4 cases) are long term survivors. We conclude that [131I]MIBG is the treatment of choice in Group 3 patient with a residual primary tumor and could contribute to consolidate the response obtained in Group 4 patients.