Development of substance dependence is influenced by multiple factors, e.g. pharmacological effects on mental status, environmental and individual factors. Among them genetic factors were found to have greater affect on substance dependence than expected which inheritance rate was calculated as 0.7 or more. However, more precise information on genetic mechanisms underlying substance dependence is still unknown. In Japan, methamphetamine has been the most popular illicit drug. The JGIDA study for genetic factors of methamphetamine dependence/psychosis started in 2001, and revealed many potential genetic predictors for individual vulnerability to methamphetamine dependence and variation of clinical phenotypes. As to susceptibility to drug dependence, 17 genetic variants were identified. A certain SNP or haplotype of the DTNBP1, GSTM1, GSTP1, glycine transporter-1 gene produce risks and that of serotonin transporter, AKT1 and CYP2D6 gene produce negative risks. As to risks of rapid onset of methamphetamine psychosis, worse prognosis or complication of spontaneous relapse, the dopamine D2 receptors, dopamine transporter, monoamine oxidase-A, catechol-O-methyltransferese, SOD2, NQO2, PICK1 gene were identified. Odds ratios of these positive or negative risks ranged from about 0.2 to 15. These findings must be informative for drug dependence rehabilitation programs and psycho-education of substance dependence.