Achieving a cure for metastatic neuroblastoma remains a challenge despite sensitivity to chemotherapy and radiotherapy. Most patients achieve remission, but a failure to eliminate minimal residual disease (MRD) often leads to relapse. Immunotherapy is potentially useful for chemotherapy-resistant disease and may be particularly effective for low levels of MRD that are below the threshold for detection by routine radiological and histological methods. Disialoganglioside (GD2), a surface glycolipid antigen that is ubiquitous and abundant on neuroblastoma cells is an ideal target for immunotherapy. Anti-GD2 monoclonal antibodies currently form the mainstay of neuroblastoma immunotherapy and their safety profile has been well-established. Although responses in patients with gross disease have been observed infrequently, histologic responses of bone marrow disease are consistently achieved in >75 percent of patients with primary refractory neuroblastoma. The advent of highly sensitive and specific molecular assays to measure MRD has confirmed the efficacy anti-GD2 antibody immunotherapy in patients with subclinical disease. Such markers will allow further optimization of other anti-MRD therapies. We review the current status of anti-GD2 clinical trials for neuroblastoma and novel preclinical GD2-targeted strategies for this rare but often lethal childhood cancer.