The inter-individual and inter-ethnic variations in phase I enzyme activity is largely attributed to gene poly-morphisms. The distribution and clinical consequences of these variations have been extensively studied in Africans, Asians, and Caucasians. However, information is still lacking regarding the frequency and the impact of these variations on xenobiotic metabolism and disease processes in Mexican Americans. Therefore, this review addresses the polymor-phisms of genes encoding phase I enzymes in Mexican Americans; these include: cytochrome P450 (CYP) 2C19,CYP2D6,CYP2E1, alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH). This review article summarizes the association between phenotype (drug metabolism) and genotype for CYP2C19 and CYP2D6 as well as the role of ge-netic variations in CYP2E1,ADH, and ALDH as potential risk factors for alcoholism in the Mexican American population. The major findings are as follows: (1) Mexican Americans have unique genetic patterns compared with other ethnic groups; (2) In general, Mexican Americans tend to be extensive metabolizers of substrates for CYP2C19 and CYP2D6; (3) Genotypes of CYP2D6 can be used to predict phenotypes in Mexican Americans; and (4) Variations in alcohol me-tabolizing genes contribute to alcoholism in the Mexican American population.