Throughout their evolution, animals have been exposed to plant and microbial secondary metabolites, which they cannot completely metabolize and utilize for their own life processes. Thus, enzyme systems enabling detoxication and removal of multiple "foreign" or "xenobiotic" compounds from the body have evolved, which have relatively low activities and broad substrate specificities. Many of these xenobiotic compounds are biologically active and are used as drugs (e.g., digitalis, morphine, tetracycline, etc.), or as pesticides (e.g., pyrethrins), while others, including compounds such as benzo(a)pyrene (BaP) and heterocycles produced by pyrolysis of plant materials, are cytotoxic. Many thousands of xenobiotic compounds have been produced in the 20th century as a result of exploitation of petroleum, and the ultimate sink for many of them is the aquatic environment. Therefore, aquatic animals have become increasingly exposed to industrially derived xenobiotic pollutants. This chapter will focus upon enzyme systems involved in the detoxication of these xenobiotic compounds.