The majority of aggressive forms of the childhood tumor neuroblastoma can with current treatment protocols not be cured and possess a major challenge in pediatric oncology. After initial rounds of chemotherapy, surgery and irradiation, which in most cases result in tumor regression, these aggressive neuroblastomas relapse and frequently develop drug resistance. As approximately 50% of the children with neuroblastoma have an aggressive form, there is a compelling demand for new treatment strategies. Arsenic trioxide has the capacity to kill multidrug-resistant neuro-blastoma cells in vitro and in vivo and the drug is currently being evaluated in clinical trials. In this report we discuss the background to the use of arsenic trioxide in cancer therapy and the currently known mechanisms by which arsenic trioxide kills human neuroblastoma cells.