As a complex (or polygenic) genetic trait, essential hypertension is determined by the interplay between many genetic variants and several environmental factors. Despite an enormous and continuous effort from the clinical and research communities, much of the genetics of essential hypertension remains elusive.1 The classic approach for identifying disease-causing genes, that is, linkage analyses, brought to the identification of genes responsible for genetic—and thus rare—forms of hypertension2; in contrast, the candidate gene approach has led to results that are subject to controversy and definitely less straightforward than those from linkage analysis. As a matter of fact, essential hypertension is a multifactorial and multigene disease, and thus the study of its etiology must be approached with complex bioinformatic and biostatistic techniques for studying gene-environment interaction and synergism among many hypertension-associated single nucleotide polymorphisms (SNPs). Given its multifactorial nature, a single SNP may be able to modify the disease phenotype only together with other SNPs and in an appropriate environmental context. Article see p 381 MicroRNAs (or miRs) are now considered fundamental components of the regulatory system of eukaryotic gene expression.3,4 They act posttranscriptionally through cis -regulatory sites, located typically in 3′-untranslated regions (UTRs) of mRNAs, usually significantly reducing protein expression without completely inhibiting the targeted mRNAs.5 Interestingly, more than 20 000 SNPs of miRNA target sites have been catalogued thus far6 and, over the last …