Over 40 cytochrome P450 (CYP) 2D6 allelic variants have been discovered thus far. The alleles may be classified on the basis of the level of activity for which they encode CYP2D6 enzymes, into functional, non-functional and reduced function groups. CYP2D6 allele frequency is known to vary amongst racial/ethnic groups. Generally, for European Caucasians and their descendants, the functional group of alleles are predominant, with a frequency of 71%. Non-functional alleles represent 26% of the variability, mainly CYP2D6*4. In Asians and their close descendants, functional alleles represent only ~ 50% of the frequency of CYP2D6 alleles. Asians and Pacific Islanders have a high frequency (median = 41%) of a reduced function allele, CYP2D6*10, contributing to the population shift to the right of metabolic rates indicating slower metabolism. Information concerning Amerindians from North (Canada), Central and South America indicate comparatively low frequencies of CYP2D6*10, perhaps a "founders" effect. The frequency of functional alleles in Africans and African Americans is also about 50%. Both Africans and African Americans have reduced function alleles representing 35% of allele variation, mainly CYP2D6*17. African Americans, however, have more than twice the median frequency of nonfunctional alleles compared with Africans (14.5% vs 6.3%). Non-functional and reduced function alleles represent about 50% of allele frequency in Black populations but a much greater variety than carried in Asians. Since alleles which encode for no or reduced functioning clearly affect metabolic activity of drugs mediated by CYP2D6, studies are needed in populations in which these alleles play a major role in order to assure optimal dosing recommendations are based on empirical pharmacogenetics.