Oxidative stress and accumulation of free radicals might play a role in the pathogenesis of vitiligo. Glutathione S-transferase (GST) is a multigene family of enzymes that detoxify oxidative stress products. In this study, genotyping by multiplex PCR of GSTM1 and GSTT1 in 101 women with nonsegmental vitiligo vulgaris and 101 age-matched healthy female volunteers showed that only the GSTM1 null genotype (P = 0.04) was significantly overexpressed in patients with vitiligo. Analysis of the combined effect of GSTM1 and GSTT1 genotyping identified a significant association of risk for vitiligo with the GSTT1/GSTM1 double-null type only (P = 0.01; OR = 2.69; 95% CI 1.12–6.46). Age of onset of vitiligo was significantly earlier in patients with the T1 null genotype (P < 0.01) and those with the T1−/M1+ and T1−/M1− combined genotypes (P < 0.01 and P = 0.01, respectively). In conclusion, the GSTM1 gene and the GSTM1/GSTT1 double-null genotype may be a risk factor for vitiligo in Egyptian patients. Inability to cope with oxidative stresses because of GST deficiency may cause early disease onset.