Possessing blood pressure in normal ranges is considered healthy, and does not warrant medical attention for obvious clinical reasons. However, to realize normotension and then maintain it even when confronted with a hypertensive threat must have its biological ‘shield of armour’. While sensitivity to hypertension has been widely recognized and studied, inherent mechanisms that enable a physiological resistance to hypertension to occur have received little attention. Recent advances in normotension genetics have produced unexpected insights. A hypertension ‘suppressor’ likely inhabits the normotensive genome of inbred Lewis rats. This suppressor behaves as a ‘master’ control capable of functionally abrogating the effects of hypertension-promoting alleles from multiple quantitative trait loci. This conceptual advancement lays the foundation for uncovering an anti-hypertension gene. Discovering its identity will assist our attempts at developing innovative diagnostic and therapeutic strategies for circumventing and treating hypertension. This new domain of suppressing hypertension goes beyond the conventional pharmacological treatments of hypertension before symptoms appear. For this purpose, a valid theoretical basis and framework is needed that can interpret the experimental data and produce testable predictions for authenticating, enriching or amending the normotension paradigm in the future.