Cytochrome P450 (CYP) 2B6 (CYP2B6) is a human CYP isoform found in variable amounts in the liver and other organs. It is known to be inducible and polymorphic and has a wide range of xenobiotic substrates. Studies of CYP2B6 to date have concentrated heavily on clinical drugs. In the present communication, however, we concentrate on its role in the metabolism of environmental xenobiotics. The term environment is used, in its broadest sense, to include natural ecosystems and agroecosystems as well as the industrial and indoor domestic environments. In essence, this excludes only clinical drugs and drugs of abuse. Many of these chemicals, including agrochemicals and industrial chemicals, can serve as substrates, inhibitors and/or inducers of CYP2B6, these activities being often modified by the existence of polymorphic variants. Metabolism-based interactions between environmental chemicals are discussed, as well as the emerging possibility of metabolic interactions between environmental chemicals and clinical drugs.