In the last decade, the most important factor in the rekindled interest in immune therapy for cancer is the development of new methods to identify tumor antigens that can be recognized by T-cells and other immune effectors. In addition, greater knowledge about tolerance and mechanisms of tumor cell evasion from immune effectors has made the prospect of developing clinically effective immune therapies for cancer seem promising. Research in immune therapies for sarcoma has been limited, mainly because of the previous lack of defined tumor antigens in this disease and the low prevalence of sarcoma in the general population. We will review the fundamental concepts of tumor immunobiology, both cellular and humoral, and highlight the new, powerful methods for identifying novel tumor antigens. Further, we will focus on the unique situation presented by sarcoma as the only solid tumor in which many cytogenetic abnormalities have been characterized which encode for unique, tumor-specific fusion proteins that are ideal targets for immune-based therapy. We will review the specifics of vaccine therapy approach to this disease, with emphasis on strategies to improve the immunogenicity of newly defined tumor antigens in sarcoma.