A growing problem of major proportions had been confronting biomedical scientists for many decades. Until solved, this long-neglected problem, the abject failure of the American health care system, presents a gigantic obstacle to the application of the discoveries flowing from neuropsychopharmacological research into deliverable medications utilized by medical practitioners. Although it is recognized that such advances could benefit all of society, both in the United States and globally, progress toward this important goal has not happened. As I noted 5 years ago, ‘Unless steps are taken soon to undertake a comprehensive restoration of our system, the profound advances in bio-medical research so rapidly accruing today may never be effectively transformed into meaningful advances in health care for society.’ I remain perplexed and frustrated by the reluctance of scientific research societies such as our ACNP to engage their energies and intellect into this most serious issue.

My goals for this perspective are to enumerate what I consider to have been the major discoveries in the investigations of the central catecholamine neuron systems from the synaptic, cellular and systems physiological and neurohistochemical perspectives. To do so, I will emphasize here the synaptic and physiological aspects of the central noradrenergic (NE) system, considering both the past research and what we may expect to witness in the decades ahead.