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 both susceptibility to essential hypertension and interindividual variation in blood pressure. A polymorphism (825C/T) in exon 10 of the GNB3 gene, that encodes for the beta3 subunit, has recently been described. The 825T allele is associated with alternative splicing of the gene and formation of a truncated but functionally active beta3 subunit. Carriers of the 825T allele appear to have an increased risk for hypertension, obesity, insulin-resistance and left ventricular hypertrophy. Moreover, 825T allele carriers respond with a stronger decrease in blood pressure to therapy with a thiazide diuretic and with clonidine. GNB3 825T allele may be regarded as a potential genetic marker for a better definition of the risk profile of hypertensive subjects, but further studies are needed to precisely define the impact of T allele on the prognosis of such patients.