Neuroblastoma is, at the same time, the most common and the most puzzling extracranial solid tumour in childhood, being able to regress spontaneously despite widespread dissemination, showing a striking high incidence of the in situ form, and, finally, being resistant even to aggressive chemotherapy. The reasons of this bizarre behaviour are still largely unknown due to our little knowledge of neuroblastoma pathophysiology. There is increasing body of evidence that the insulin-like growth factor system plays a crucial role in the proliferation and differentiation of neuroblastoma cells and it is conceivable that a better knowledge of this role might potentially lead to new and more effective therapeutic strategies. Here we review the most recent insights into the biology of neuroblastoma, focusing on the close links with the insulin-like growth factor system and the potential clinical perspectives.