Aldehyde dehydrogenase 2 (ALDH2) is a member of ALDH family. ALDH1 has been widely recognized for its roles in carcinogenesis and cancer therapy; however, investigation for ALDH2 in cancer is seldom mentioned. The ALDH2 point mutation ALDH2*2 is the most frequent human gene variant, and it is present in approximately 560 million East Asians. ALDH2*2 demonstrates its effect on alcohol consumption limiting and alcoholism developing protection, and this variant is recently found to have an important impact on human health. This chapter focuses on its potential effect on cancer therapy, especially for chemotherapeutics with anthracyclines.