This chapter investigates how animals detect airborne or waterborne chemicals. The strategy used by both humans and flies resembles how the human immune system detects foreign epitopes on the surfaces of invading microbes. That strategy entails using proteins as "feature detectors" and then merging the features into a composite representation at higher brain levels. The logic is reminiscent of the proverbial blind men who are sampling different parts of an elephant. The most striking similarity in the chemosensory systems of humans and flies concerns how olfactory information is processed. In both cases, sensory neurons that expres the same olfactory receptor (OR) protein send their axons to the same glomerulus. Glomeruli are spherical clusters of neurons that act as the first waystation for olfactory input, and they are found in either the olfactory lobe (humans) or antennal lobe (flies). Glomeruli serve in part to boost the signal: the ratio of sensory neurons to glomeruli is ~50:1 for flies and ~5000:1 for mice. There are ~1000 functional OR genes in mice, ~400 in humans, and only ~60 in fruit flies. The latter number may be small because their diet is so restricted.