While most of the focus in cancer immunology is on CD8+ cytotoxic T lymphocyte responses, recent evidence indicates that CD4+ T cells are an equally critical component of the antitumor immune response. Successful immunity to cancer will therefore require activation of tumor-specific CD4+ T cells. Tumor antigens recognized by CD4+ T cells that are restricted by MHC class II are beginning to be defined in both murine and human tumors. These will provide the basis for new generations of antigen-specific tumor vaccines.