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β2-Adrenoceptors (AR) play an important role in regulation of vascular and bronchial smooth muscle tone; functional β2-AR, however, also exist in human heart where they can mediate positive inotropic and chronotropic effects. Recent studies have discovered that β2-AR are polymorphic. The most common single nucleotide polymorphisms (SNPs) are: Arg16Gly, Gln27Glu, Thr164Ile in the coding region, and Arg-19Cys in the 5′ upstream peptide. These SNPs affect receptor function in vitro; however, conflicting data exist on their functional relevance in vivo. This might be due to the fact that the four SNPs in the 5′ upstream peptide and in the coding region, respectively, are linked and form certain haplotypes. This review gives an overview on the contribution of β2-AR polymorphisms to cardiovascular diseases or altered drug responses. In addition, the relevance of SNPs vs. haplotypes for β2-AR functional responsiveness is discussed.