In vertebrate olfactory transduction, a Ca(2+)-dependent Cl(-) efflux greatly amplifies the odorant response. The binding of odorants to receptors in the cilia of olfactory sensory neurons activates a transduction cascade that involves the opening of cyclic nucleotide-gated channels and the entry of Ca(2+) into the cilia. The Ca(2+) activates a Cl(-) current that, in the presence of a maintained elevated intracellular Cl(-) concentration, produces an efflux of Cl(-) ions and amplifies the depolarization. In this review, we summarize evidence supporting the hypothesis that anoctamin 2/TMEM16B is the main, or perhaps the only, constituent of the Ca(2+)-activated Cl(-) channels involved in olfactory transduction. Indeed, studies from several laboratories have shown that anoctamin 2/TMEM16B is expressed in the ciliary layer of the olfactory epithelium, that there are remarkable functional similarities between currents in olfactory sensory neurons and in HEK 293 cells transfected with anoctamin 2/TMEM16B, and that knockout mice for anoctamin 2/TMEM16B did not show any detectable Ca(2+)-activated Cl(-) current. Finally, we discuss the involvement of Ca(2+)-activated Cl(-) channels in the transduction process of vomeronasal sensory neurons and the physiological role of these channels in olfaction.