Apolipoprotein E (APOE) is a lipid transfer protein, which plays an important role in maintaining the stabilization of nerve and recovering. Alzheimers disease (AD) is a neurodegenerative disorder. Most studies showed that APOE genotypes were closely related with AD. In clinical practice, AD is mainly manifested as progressive cognitive decline, and often accompaniedmental behavioral symptoms. These symptoms also exist in common severe mental illness. It is worth thinking about the correlation between APOE genotypes and these diseases. This article reviewed the relationship between the APOE genotypes and the common major psychosis.