Tumor-associated gangliosides have been investigated for their potential as antigenic targets for more than 35 years, culminating in the recent Food and Drug Administration approval of dinutuximab (Unituxin), an IgG antibody targeted against GD2, for the treatment of neuroblastoma in children. This review is focused on discoveries and development of therapeutic approaches involving human IgM antibodies directed against gangliosides, which occurred over the past 40 years at University of California-Los Angeles and the John Wayne Cancer Institute, where Dr. Donald Morton led the surgical oncology department until his death.