Odorant receptors are encoded by extremely large and divergent families of genes. Each receptor is expressed in a small proportion of neurons in the olfactory organs, and each neuron in turn expresses just one odorant receptor gene. This fundamental property of the peripheral olfactory system is widely conserved across evolution, and observed in vertebrates, like mice, and invertebrates, like Drosophila, despite their olfactory receptor gene families being evolutionarily unrelated. Here we review the progress that has been made in these two systems to understand the intriguing and elusive question: how does a single neuron choose to express just one of many possible odorant receptors and exclude expression of all others?