The sense of smell is the least understood of all human senses. The olfaction process is a complex one involving both physiological peripheral sensing and cognitive and emotional central processing. The olfactory receptor neurons are situated in the olfactory epithelium located in the upper portion of the nasal cavity. These cells project cilia into the mucus lining of the nasal cavity, and those are responsible for the first stages of the olfaction process. The binding of an odor molecule to the receptor results in an electrical signal that is transducted through the neuron’s axon to the olfactory bulb, and causes the release of a neurotransmitter (Berkowicz et al. 1994), which activates mitral and tufted cells within the olfactory bulb to carry the information further into the brain. Within the brain, the olfactory system is closely linked to areas of the brain that are involved with emotion (i.e., Amygdala) (Cain and Bindra 1972; Zald and Pardo 1997), memory, and learning (i.e., the hippocampus).

We do not yet completely understand which odorants activate a certain receptor. However, it seems that different combinations of olfactory neuron activation may have the potential to explain the large variety of detectible odors. Research has shown that different receptors families are expressed zonally across the olfactory epithelium (Strotmann et al. 1994), which coincides with zones of odorant sensitivity. This may suggest that odor qualities are coded at the level of the olfactory bulb on the basis of distributed patterns of activity (Shepherd 1994).

Genetic variations in human odorant receptors may account for the vast differences in odor perception between different individuals (Keller et al. 2007). Furthermore, genetic differences in receptor expression may help to explain why some individuals with a normal sense of smell may be “blinded” to a single odorant or a small group of closely related odorant (i.e., specific anosmia) (Amoore 1977). However, repeated exposure to an odorant did seem to induce the ability to detect it by subjects who were initially anosmic to it (Dorries et al. 1989).

Research has shown that a certain amount of electrical activity is always present in the olfactory neurons. This activity is referred to as baseline “noise” (Cain 1977), and is considered to increase olfaction sensitivity on the expense of specificity. This implies that the receptors are easily activated by minute concentration of odorants even with marginal odorant–receptor fit.

The response to a certain odorant is terminated, presumably to allow the system to be ready for the next stimulus. This process (i.e., adaptation) occurs both peripherally at the receptor cell, and centrally in the brain. At the receptor cell level, olfactory adaptation is calcium dependent (Kurahashi and Menini 1997), therefore this process may be affected by medications or conditions that affect cellular calcium homeostasis. Central adaptation mechanism is not yet understood. However, unlike receptor cell adaptation that is considered short term (minutes), central adaptation may last for as long as 4 weeks (Dalton and Wysocki 1996).

Various diseases and conditions may affect olfactory function. For example, research has shown that the neurotransmitter dopamine decreases the baseline activity (i.e., “noise”) of mitral cells in the olfactory bulb (Duchamp-Viret et al. 1997). Therefore, in patients with Parkinson’s disease in which dopamine synthesis is impaired, the ability to identify odors may be reduced (Doty et al. 1991). These patients’ olfactory disorder was shown to be independent of the cognitive, perceptual-motor, and memory manifestations of the disease (Doty et al. 1989).

Most studies conducted on the relationship between gender and olfaction have concluded that at least for some odorants, females perform better than males in odor detection, identification, and discrimination (Doty and Cameron 2009). Estrogen modulates the activity of retinoic acid, an important factor in olfactory cells differentiation (Balboni et al. 1991). This might explain the observation that premenopause females tend to perform better than males in olfactory function tests (Wysocki and Gilbert 1989). However, a recent systematic review that examined the data about sex hormone alterations (e.g., menstrual cycle, pregnancy, gonadectomy, and hormone replacement therapy) and human olfactory function concluded that the relationship between the two is complex and any simple explanation for any association between them is tenuous (Doty and Cameron 2009). One recent study showed that females of three different age groups (19–39, 40–59, >60) performed significantly better than males for both odor threshold and odor discrimination, thus demonstrating higher olfactory sensitivity (Thuerauf et al. 2009). The researchers attributed this to the link between odors and emotional reactivity, since females demonstrated better emotion-linked memory (Canli et al. 2002).

Cognitive factors have been shown to impact human odor perception. Research showed that subjects who were given a negative description of an odor gave higher intensity scores, perceived it as irritating, and were less adaptive to it than those who were given a neutral or positive description (Dalton et al. 1997).

Taken together, these physiological and environmental factors may help to explain the high intra- and inter-individual variability seen in psychophysical research on olfactory threshold (Stevens et al. 1988).

Naturally occurring smells such as breath odors are usually a complex mixture of various odorants. Unlike some other sensory systems in which the intensity of a complex signal is the sum of its components (i.e., additivity), in olfaction this rule does not seem to apply. Studies done on two component mixtures show that in most cases, mixing the odorants results in the suppression of the perceived intensity of one or both odors (Laing et al. 1984). Although the strength of an odor may be increased by the presence of another (i.e., synergism), this is rarely seen in two component mixtures. However, some researchers have reported a substantial synergistic effect in a complex mixture of many odorants (Laska and Hudson 1991) at concentration too low to be sensed individually (i.e., subthreshold).

Some studies have been conducted on the interactions of unpleasant odor components (Berglund 1974