During the last years was observed that adverse drug reactions have a leading position in mortality causes. Many adverse reactions can be explained by hereditary factors including the polymorphism of cytochrome P450 isoenzymes. The cytochrome P450 CYP2D6 enzyme metabolizes approximately 25% of current drugs including some beta-blockers. The aim of the study was to analyze the literature data about the importance of cytochrome P450 CYP2D6 genetic polymorhism in beta-blockers therapy. Materials and methods: Studies about relationship between CYP2D6 genetic polymorphisms and betablockers therapy were selected from PubMed. Results: In comparison with other beta-blockers, metoprolol has the most CYP2D6 dependent metabolism. Recent data (Blake C.M. et al. 2013, Bijl M.J. et al. 2009) suggest that CYP2D6 poor metabolizers have increased rate of adverse reactions when treated with metoprolol. Studies show that bisoprolol has a relatively constant beta-adrenergic inhibition independent of CYP2D6 genotype. In other studies, authors (Lindamood C. 2010, Lefebre J. et al. 2006) concluded that CYP2D6 polymorphism significantly influenced the metabolism of nebivolol, but not its efficacy and tolerability. That similar clinical response between CYP2D6 extended metabolizers and poor metabolizers could be explained by the contribution of active metabolites of nebivolol to its cardiovascular actions in extended metabolizers. Conclusions: Some beta-blockers (metoprolol, carvedilol) need to be used cautiously in CYP2D6 poor metabolizers, while others are relatively safe and well tolerated (bisoprolol, nebivolol).