In the development of novel immune therapies for high-risk cancers, one goal is to find tumor targets that are not widely shared by normal cells. One such target is the surface disialoganglioside GD2. This antigen is expressed on the surface of a variety of tumors for which no curative therapies exist for patients with advanced disease. In childhood, the most common GD2-expressing tumor is neuroblastoma. GD2 is also expressed on several other high-risk tumors, including those of neuroectodermal or epithelial origin, virtually all melanomas, and approximately 50% of tumor samples from osteosarcoma and soft-tissue sarcomas. Because of the tumor-selective expression of this molecule, it is an attractive target for tumor-specific therapies such as antibody therapy. Over the last 2 decades, several anti-GD2 antibodies have been developed. To reduce both the toxicity of the antibody and the development of human anti-mouse antibodies (HAMA), research efforts have primarily focused on exploring anti-GD2 antibodies that have progressively more human elements while at the same time reducing the mouse components. This review will examine antibodies currently undergoing clinical testing as well as the most recent advances to improve antibody therapy for patients with GD2-expressing tumors.