Children with high-risk neuroblastoma who fail to achieve adequate metastatic response after induction chemotherapy have dismal outcome and new therapeutic strategies are needed. However, timing of introduction of novel agents still remains under discussion. Given an increase in number of phase I-II studies of molecularly targeted drugs in neuroblastoma, it is crucial to determine, as early as possible, which patients may be suitable candidates for new therapeutic strategies. This single-center retrospective analysis of patients with high-risk neuroblastoma showed that the addition of conventional chemotherapy improved the quality of metastatic response only for the group of patients with partial response. It is therefore proposed to develop stratification criteria for those patients very unlikely to benefit from a plethora of additional lines of treatment, but might benefit from introduction of novel agents.