The olfactory system is an essential part of human physiology, with a rich evolutionary history. Although humans are less dependent on chemosensory input than are other mammals (Niimura 2009, Hum. Genomics 4:107–118), olfactory function still plays a critical role in health and behavior. The detection of hazards in the environment, generating feelings of pleasure, promoting adequate nutrition, influencing sexuality, and maintenance of mood are described roles of the olfactory system, while other novel functions are being elucidated. A growing body of evidence has implicated a role for olfaction in such diverse physiologic processes as kin recognition and mating (Jacob et al. 2002a, Nat. Genet. 30:175–179; Horth 2007, Genomics 90:159–175; Havlicek and Roberts 2009, Psychoneuroendocrinology 34:497–512), pheromone detection (Jacob et al. 200b, Horm. Behav. 42:274–283; Wyart et al. 2007, J. Neurosci. 27:1261–1265), mother–infant bonding (Doucet et al. 2009, PLoS One 4:e7579), food preferences (Mennella et al. 2001, Pediatrics 107:E88), central nervous system physiology (Welge-Lüssen 2009, B-ENT 5:129–132), and even longevity (Murphy 2009, JAMA 288:2307–2312). The olfactory system, although phylogenetically ancient, has historically received less attention than other special senses, perhaps due to challenges related to its study in humans. In this article, we review the anatomic pathways of olfaction, from peripheral nasal airflow leading to odorant detection, to epithelial recognition of these odorants and related signal transduction, and finally to central processing. Olfactory dysfunction, which can be defined as conductive, sensorineural, or central (typically related to neurodegenerative disorders), is a clinically significant problem, with a high burden on quality of life that is likely to grow in prevalence due to demographic shifts and increased environmental exposures. Clin. Anat. 27:54–60, 2014. © 2013 Wiley Periodicals, Inc.