During cancer progression, many somatic mutations accumulate in cancer cells. Antigens derived from tumor-specific mutated genes are primary sources ofneoantigens in cancer immunology. As compared with non-mutated self-antigens, neoantigens are thought to have higher antigenicity, and are expected to be ideal targets for tumor rejection. Recent studies demonstrate that T cells recognize neoantigens and elicit immune responses against tumor cells. The importance ofneoantigens in cancer immunity has been well acknowledged, and development ofneoantigen -targeted cancer immunotherapy is in progress worldwide. High-throughput detection ofsomatic mutations by whole-exome sequencing is combined with computational algorithm for MHC-peptide binding affinity to predict potential neoantigens. After the antigenicity is confirmed by immunological assays, personalized vaccines targeting the identified neoantigens will be generated with peptides, dendritic cells, or RNAs. Such neoantigen-targeted cancer vaccines are being developed for practical use. In fact, several clinical trials have already been initiated in Europe and the US.