After decades of investigation, the causes of essential hypertension remain obscure. The contribution of the nervous system has been excluded by some on the basis that baroreceptor mechanisms maintain blood pressure only over the short term. However, this point of view ignores one of the most powerful contributions of the brain in maintaining biological fitness-specifically; the capacity to promote adaptation of behavioral and physiological responses to cope with new challenges and maintain this new level of activity through processes involving neuroplasticity. This review presents a body of recent findings demonstrating that experiences encountered earlier in life can produce persistent conditions resulting in an enhanced blood pressure response to hypertension-eliciting stimuli. This sensitized hypertensinogenic state is maintained in the absence of the inducing stimuli, and it is accompanied by sustained up-regulation of components of the brain renin-angiotensin-aldosterone system and other molecular changes recognized to be associated with central nervous system neuroplasticity. While the heritability of hypertension is high, it is becoming increasingly clear that factors beyond just genes contribute to the etiology of this disease. Life experiences and attendant changes in molecular components in the neural network controlling sympathetic tone can enhance the hypertensive response to recurrent, sustained or new stressors. Although the epigenetic mechanisms that allow the brain to be reprogrammed in the face of challenges to cardiovascular homeostasis can be adaptive, this capacity can also be maladaptive under conditions present in different evolutionary eras or ontogenetic periods.