It is a fact that sympathetic outflow is a player in most, if not all, hypertensive conditions. A selective, effective, and relatively benign means of controlling it remains high on every clinician's wish list. In this supplement we examine the neurobiologic and pharmacologic evidence that the wish is nearing fulfillment. Recent evidence has documented the existence of nonadrenergic receptors in the brainstem, other than the well-known alpha 2-adrenergic receptors, that bind the imidazoline portion of vasoactive molecules. Pharmacologic science has wasted little time in developing compounds rich in imidazoline-like structures that, by supplanting norepinephrine (the natural cerebral neurotransmitter for sympathetic nervous system outflow) quiet sympathetic outflow, restrain heart rate and vasomotor influence, and reduce the negative quality-of-life effects induced by earlier centrally acting agents. This is because specific ligands for the imidazoline-preferring receptors appear to lower blood pressure without attendant drowsiness, dry mouth, and impaired mentation. Rilmenidine, the subject of this supplement, is the newest such agent, and the scientists involved in its development and clinical trials have produced heartening data. These developments presage good news in the clinic, and I am excited by their potential, particularly that for gaining deeper insight into human pressor phenomena.