Neuroblastoma (NBL) is the most common extracranial solid tumor in pediatrics, yet overall survival is poor for high-risk cases. Immunotherapy regimens using a tumor-selective antidisialoganglioside (anti-GD2) monoclonal antibody (mAb) have been studied for several decades now, but have only recently been incorporated into standard of care treatment for patients with high-risk NBL with clear benefit. Here we review a brief history of anti-GD2-based immunotherapy, current areas of neuroblastoma research targeting GD2, and potential diagnostic and therapeutic uses targeting GD2.