MAGE A4 (Melanoma Antigen Gene A4) is a cancer testis antigen (CTA) that is expressed normally in germline cells (testis/embryonic tissues) but absent in somatic cells. The MAGE A4 CTA is expressed in a variety of tumor types, like synovial sarcoma, ovarian cancer and non-small cell lung cancer. Having its expression profile limited to germline cells has made MAGE A4 a sought-after immunotherapeutic target in certain malignancies. In this review, we focus on MAGE-A4's function and expression, current clinical trials involving targeted immunotherapy approaches, and challenges and opportunities facing MAGE-A4's targeted therapeutics.