Melanoma is a highly malignant tumor. Prognoses of melanoma patients are often unsatisfactory due to poor operational and chemoradiational efficacy. Recently, researches for melanoma treatment have found multipeptide vaccines a favorite and possible breakthrough as they are stable in chemical property and easy to be synthesized, have no carcinogenecity and dispense with virus vector. Studies have shown that the immunogenicity of multipeptide vaccines could be enhanced by use of immunoadjuvants, joining dendritic cells (DCs), full-length or epitope-superposited antigen peptides, costimulatory molecules and cellpenetrating peptides fusion, thereby improving anti-tumor effect. Certain achievements have been obtained in clinical treatment of melanoma by multipeptide vaccines, but problems including poor immunogenicity and human leukocyte antigen (HLA) phenotype restriction may require further study.