The Environmental Genome Project (EGP) has generated a comprehensive resource of commonly occurring single nucleotide polymorphisms (SNPs) in more than six hundred environmental response genes, including a number of drug metabolism genes. The gene-oriented sequence variation discovery carried out by the EGP is complementary to the HapMap and enables genome-wide association studies (GWAS) that survey a large portion of the known common variation. For GWAS focused on drug metabolism genes and phenotypes, it is important to know the proportion of common SNPs covered by the commercially available high-throughput genotyping chips. Herein, we review a subset of Phase I cytochrome P450 genes studied by the EGP, approaches to GWAS, and the sensitivity of available genotyping platforms to capture common sequence variation in this subset of drug metabolism genes.