Hypertension is a common disorder of multifactorial origin that constitutes a major risk factor for cardiovascular events such as stroke and myocardial infarction. The subunits of the heterotrimeric G proteins are attractive candidate gene products for susceptibility to hypertension, obesity and insulin resistance syndrome. A polymorphism (825C/T) in exon 10 of the GNB3 gene, encoding for the Gβ3 subunit, has been described. The 825T allele is associated with alternative splicing of the gene and formation of a truncated but functionally active β3 subunit. Many studies have investigated whether carriers of the 825T allele are at increased risk for hypertension, obesity, insulin-resistance and left ventricular hypertrophy with apparently conflicting results. The present review demonstrates that GNB3 825T allele is a useful genetic marker for better defining the risk profile of hypertensive patients, as it is associated with increased risk of stroke and myocardial infarction in longitudinal studies in Caucasians.