Recent immunotherapy depends largely on understanding of the molecular interactions between T cell receptors (TCR) on cytotoxic T lymphocytes (CTL) and peptide/MHC class I complexes on tumor cells. Many tumor antigens identified by cDNA library expression cloning methods, especially from malignant melanoma, have greatly contributed to clarifying such mechanisms and led to peptide vaccination trials, mainly for patients with melanoma. Although the objective tumor regression rate mediated by peptide vaccination is still low compared to adoptive cell transfer therapy, antigenic peptide vaccination can cause a constant objective response generally evaluated as stable disease or decreased serum levels of tumor markers. In addition, recent trials in the adjuvant setting showed some suppressive effects against recurrence. Therefore, peptide vaccination still has potential for clinical benefits in patients with various cancers. For further improvement of peptide vaccination, we considered that (i) novel antigenic peptides, (ii) effective adjuvants, (iii) more sensitive immunological monitoring and (iv) drugs up-regulating HLA class I molecules might be important.