Cytochrome P450 2D6 (CYP2D6) is an enzime which participates in the first phase of biotransformation of xenobiotics and endogenous molecules. It is responsible for the metabolism of more than 25% drugs. CYP2D6 gene is located on chromosome 22, locus 22q13.1 and it contains 9 exons encoding 497 amino acids. Characteristic of CYP2D6 gene is its pronounced susceptibility to variabilities which is important in clinical practice, because CYP2D6 is involved in the metabolism of a large number of drugs. CYP2D6 polymorphisms are characterized by four metabolic phenotypes. Normal metabolizers are present in approximately 60 – 75%, and intermediate metabolizers in 25 – 40% of the population. The incidence of slow metabolizers is 5 – 10% in white and black African populations, and 1% in Asians. Ultra rapid metabolizers are present in 1 – 10% of the white population. The most common non–functional allele is CYP2D6*4 and is found in approximately 20% of Europeans, while it is almost absent in Asians. In Asians, the allele of reduced function CYP2D6*10 (40%) is the most common. Genetic variability of CYP2D6 gene may significantly affect the outcome and efficacy of therapy with drugs metabolized by CYP2D6. In slow metabolizers, the plasma concentration of drug is increased, which may induce the development of harmful side effects. To prevent the development of side effects, it is recommended to reduce the dose of a drug in slow metabolizers. On the other hand, in ultra rapid metabolizers, plasma drug concentration is reduced and this may cause an inadequate response to therapy. This can be prevented by increasing the dose of a drug in ultra rapid metabolizers. Some drugs are remodeled into pharmacologically active metabolites only by the action of the enzyme CYP2D6. In that case slow metabolizers have reduced levels of active metabolites resulting in reduced therapeutic effect, and very fast metabolizers have elevated levels of active metabolite and the development of side effects is possible. Guidelines for drug selection and dosing according to an individual’s genetic profile are available.