To date, dozens of melanoma-associated antigens (MAGEs) have been identified, and classified into subgroups I and II. Subgroup I, also named as cancer/testis (CT) antigen, consists of antigens whose expression is generally restricted to tumor cells, or germ cells. Proteins and peptides derived from some of these antigens have been used in promising clinical trials for cancer immunotherapies. Although the role of MAGEs in cell activities is unclear, various MAGEs were noticed to function physiologically and pathologically during embryogenesis, germ cell genesis, apoptosis, etc. It is reasonable to speculate that the genes of subgroup I of MAGEs, after playing important roles during embryogenesis, could be deactivated by genetic mechanisms, such as methylation. In the case of tumor formation, these genes are reactivated, and the resulted proteins may be recognized and attacked by immune system. Thus, subgroup I of MAGEs may play important roles in immune surveillance of certain tumor types. Here, we have sought to review the classifications and biological functions of MAGE family genes.