Although essential hypertension is usually defined as a hemodynamic disorder, it is expressed differently among individuals and varies during progression of the disease state. Therefore, various types of treatment can be envisioned. The use of selective I1-imidazoline-receptor agonists to modulate I1-imidazoline receptors involved in the central regulation of blood pressure has led to the introduction of a novel class of centrally acting antihypertensive drugs. Moxonidine, a representative molecule of this class, dissociates between a 10% α2-adrenoceptor-agonist action linked with side effects such as fatigue or dry mouth, and a 90% specific antihypertensive action resulting from its selective agonistic action at I1-imidazoline receptors. Clinical experience is based on more than 2,000 patients and volunteers, and long-term efficacy has been demonstrated in about 500 patients who received a daily dose of moxonidine 0.2-0.4 mg. Moxonidine produces a pronounced reduction in peripheral vascular resistance without reflex tachycardia, accompanied by reduced plasma norepinephrine concentration and plasma-renin activity. Cardiovascular responses to exercise and standing remain nearly normal, and serious or life-threatening side effects, particularly the sympathetic overactivity that can occur on sudden withdrawal of other centrally acting agents, are never observed. In addition, moxonidine behaves neutrally with respect to plasma levels of cholesterol, potassium and glucose, glucose and lipid metabolism, and renal function, and can be administered without complication to patients with asthma or certain other diseases. Studies with magnetic resonance imaging have shown that moxonidine significantly reduces left ventricular mass, an indicator of left ventricular hypertrophy (LVH), within a 6-month treatment period, an effect that coincided with decreased plasma concentrations of catecholamines and renin. Comparisons between moxonidine and other well-established antihypertensive drugs such as nifedipine, atenolol, or angiotensinconverting enzyme inhibitors showed equal effectiveness in lowering blood pressure, whereas the adverse events profile always favored moxonidine. Considering its efficacy, safety, and specific effects (e.g., its ability to reduce LVH), moxonidine meets the criteria satisfied by other currently prescribed antihypertensive drugs. Because of its especially favorable benefit-to-risk ratio, moxonidine should be recommended as first-line treatment of hypertension and may also be useful in treating related problems such as LVH, coronary artery disease, and ventricular premature beats.