Neuroblastoma is one of the most common pediatric solid tumors originating from the sympathoadrenal lineage of the neural crest. The tumors found in infants very frequently regress spontaneously by differentiating and/or undergoing programmed cell death, while those in children over one year of age are very aggressive and eventually kill the patients. The recent advances in neuroblastoma research have revealed that the neurotrophin signals, especially those through nerve growth factor and its receptor, TrkA, play an important role in regulating the regression of neuroblastoma. The genetic abnormalities such as allelic loss of the distal region of chromosome 1p, gain of chromosome 17q21-q25, and MYCN amplification, all of which are associated with the tumor aggressiveness, inhibit the regression of neuroblastoma. In the regressing tumor cells, caspases are induced and surviving, which is mapped to 17q25 and is overexpressed in the advanced stage tumors, is down-regulated. Thus, the molecular mechanism of spontaneous regression of neuroblastoma is now being unveiled. However, many more questions including the developmental machinery to trigger regression still remain to be clarified.