The sense of smell is greatly underappreciated, despite the fact that it monitors the intake of airborne agents into the human respiratory system and determines to a large degree the flavor and palatability of foods and beverages. In addition to enhancing quality of life, this primary sensory system warns of spoiled foods, leaking natural gas, polluted air and smoke, and mediates basic elements of communication (eg, mother–infant interactions). It is now apparent that smell dysfunction is among the first clinical signs of such neurodegenerative diseases as Alzheimer's disease and sporadic Parkinson's disease. In this brief article, the author reviews the anatomy and physiology of this primary sensory system, means of assessing its function, and major diseases and disorders with which it is intimately associated.