Cytochrome P450s (CYPs) are a huge gene superfamily of heme enzymes involved in xenobioitc as well as endobiotic metabolism. They play a critical role in adaptation to environmental changes for survival of living organisms. In addition, the huge environmental loads of human-made chemicals are biotransformed into bioactive or detoxified forms by CYPs. Thus, CYPs have been used for biomonitoring of environmental pollutants, screening of their metabolisms and exploring remedy. In particular, the induction or inhibition of CYPs has been applied to exposure monitoring of environmental toxicants, which are biotransformed by CYPs. This review considers past and future applications of CYP-genetic polymorphisms as susceptibility biomarkers for biomonitoring. Furthermore, we suggest the needs for further understanding of the characteristics of each CYP isozyme, consideration of real-life exposures such as mixed contamination with various chemicals, and incorporation of the presence of other phase I and phase II enzymes, for proper applications of CYP polymorphisms on biomonitoring.