The cytochrome P450 (CYP) enzyme system is a superfamily of heme-containing mono-oxygenases located primarily in the liver (also in intestinal wall, kidneys, lungs) responsible for Phase I drug metabolism (oxidation, reduction, hydrolysis). Six major CYP isoforms metabolize ~90% of clinically used drugs: CYP3A4 (metabolizes ~50% of all drugs -- the most important isoform), CYP2D6 (20-25%), CYP2C9 (15%), CYP2C19 (10%), CYP1A2 (5%), and CYP2E1. Enzyme INHIBITORS decrease the metabolism of substrate drugs, increasing their plasma levels and risk of toxicity. Enzyme INDUCERS increase metabolism, decreasing plasma levels and potentially causing therapeutic failure. Genetic polymorphisms create poor metabolizers (increased drug levels, toxicity risk), extensive/normal metabolizers, and ultra-rapid metabolizers (reduced drug levels, therapeutic failure). CYP2D6 and CYP2C19 have the most clinically significant genetic polymorphisms.