The classic candidate gene approach continues to be the most prevalent tool in the search for the genetic basis of essential hypertension. With the list of candidate genes for this disorder steadily increasing, the pertussis toxin-sensitive inhibitory G protein (Gi) protein beta3 subunit (GNB3) gene has remained "sizzling," challenging the domination of the renin-angiotensin system. Is the genetic variability of GNB3 a causative factor underlying the pathogenesis of essential hypertension? Is the "functional" polymorphism, C825T, only "another" of the countless single nucleotide polymorphisms (SNP) for this disorder after all? As such, does its presence merely reinforce our confidence that essential hypertension is indeed polygenic? Should the C825T polymorphism be used in clinical practice and individualized antihypertensive treatment? Currently, there are still more questions than answers. In this review, in conjunction with our own research, we bring readers up to date on the latest developments of GNB3 polymorphisms in the field of hypertension.