The cytochromes P450 (CYP) comprise a large multigene family of hemethiolate proteins which are of considerable importance in the metabolism of xenobiotics and endobiotics. Over 500 CYP genes have been identified in prokaryotes and eukaryotes, and there are around 20 CYP subfamilies in humans [1]. However, researchers in the area of drug metabolism have traditionally focused on human CYP3A, CYP2D, CYP2C, and CYP1A subfamilies (in descending order of prominence in drug metabolism). Interestingly, the CYP2B subfamily, although widely studied in other species, has not been shown to have a significant role in drug metabolism in humans. The human CYP2B form apparently expressed in the liver, CYP2B6, has been thought to constitute only a small percentage of total hepatic P450 (0.2%[2]). According to recent research, CYP2B6 may be expressed in most individuals at a level similar to the minor CYPs like CYP2D6. Only very recently has the ability of CYP2B6 to catalyze the oxidation of a number of structurally different xenobiotics been recognized. This review aims to summarize our present understanding of this previously poorly understood and partially characterized enzyme. We indicate that a synthesis of the information obtained by studying CYP2B6 has provided further insight into its substrate requirements and enlightened us as to the varied catalytic nature of human CYPs in general.