CYP1A2 is one of the major CYPs in human liver (∼13%) and metabolises a variety of clinically important drugs, such as clozapine, lidocaine, theophylline, tacrine, and leflunomide. CYP1A2 is one of the major enzymes that bioactivate a number of procarcinogens and thus induction of CYP1A2 may increase the carcinogenicity of these compounds. This enzyme also metabolizes several important endogenous compounds including steroids, retinols, melatonin, uroporphyrinogen and arachidonic acid. In the recently published crystal structure of CYP1A2 in complex with α-naphthoflavone, its compact active site is closed without clear solvent or substrate access channels. Not surprisingly, CYP1A2 has a relatively small volume of the active site cavity of 375 Å3, which is 44.2% larger than that of CYP2A6 (260 Å3), but much smaller than that of CYP3A4 (1385 Å3) and 2C8 (1438 Å3). Generally, CYP1A2 substrates contain planar ring that can fit the narrow and planar active site of the enzyme. Like many of other CYPs, CYP1A2 is subject to induction and inhibition by a number of compounds. Similar to CYP1A1 and 1B1, CYP1A2 is primarily regulated by the aromatic hydrocarbon receptor (ÅhR), a ligand-activated transcription factor and a basic helix-loop-helix protein belonging to the Per-Arnt-Sim family of transcription factors. Knockout of Cyp1a2 in mice has provided a very useful tool for the functional investigation of this gene. Further studies are needed to explore the clinical and toxicological significance of CYP1A2.