Essential hypertension, which affects 25% of the middle-aged adult population, constitutes a major risk factor for stroke, myocardial infarction, and heart and kidney failure. 1 The kidney, vasculature, and nervous system govern the long-term control of blood pressure by regulating sodium homeostasis and peripheral resistance; they, in turn, are influenced by numerous hormones and neural and humoral factors. These hormones and neural and humoral factors can be divided into 2 groups based on their effects on sodium excretion and vascular smooth muscle contractility. One group leads to natriuresis and vasodilation whereas the other causes sodium retention and vasoconstriction. The balance between those 2 groups keeps the blood pressure within the normal range. Hypertension may be caused not only by increased activity of prohypertensive systems (for example, the renin-angiotensin system [RAS] and sympathetic nervous system) but also by defects in antihypertensive systems that serve as counterregulatory mechanisms. Aberrations in these counterregulatory pathways, which include the dopaminergic pathway, may be involved in the pathogenesis of essential hypertension. Dopamine has been shown to be an important regulator of renal and hormonal function and, ultimately, blood pressure, through an independent, nonneural dopaminergic system. 2 There is a difference in the synthesis and metabolism of dopamine in neural and nonneural cells (see following paragraphs). For example, dopamine synthesized in renal proximal tubule (RPT) cells is not converted into norepinephrine and epinephrine; it is transported across the basolateral and apical membranes and into the peritubular space and tubular lumen, respectively, where it acts on its receptors locally and in more distal nephron segments. Dopamine, by occupation of its specific receptors as well by direct or indirect interaction with other G protein–coupled receptors (for example, adenosine, angiotensin, endothelin, insulin, oxytocin, and vasopressin) and interaction with other hormones/humoral agents (for example, aldosterone, angiotensins, atrial natriuretic peptide, eicosanoids, insulin, nitric oxide, prolactin, and urodilatin) regulates water and NaCl excretion. 3, 4 During normal or moderately increased NaCl intake, inhibition of D1-like receptors decreases NaCl excretion by 60%. In hypertensive states, the dopamine-mediated inhibition of sodium transport is often impaired. Although dopamine production is diminished in a few specific hypertensive states, this is not usually the case. Indeed, renal dopamine production is increased in young hypertensive patients. This review updates the role of dopamine and its receptors in the control of normal blood pressure and in the pathogenesis of hypertension. We will provide evidence that dopamine and its receptors act as an important antihypertensive counterbalance against the prohypertensive effects of the α-adrenergic system and RAS.