Designed for general chemical recognition, the mammalian olfactory system shares many similarities with the immune system. Among these is the popular notion that a single olfactory sensory neuron expresses a single odorant receptor gene, while all other approximately 1000 genes of this type remain silent. Here, I examine the evidence supporting the one receptor-one neuron hypothesis. I conclude that, contrary to widespread belief, it is far from being proven. I propose an hypothesis of a developmental phase of oligogenic expression that is followed by positive and negative selection resulting usually in cells with one expressed receptor. Curiously, selective processes are well established and widely accepted for lymphocytes, but these concepts are essentially ignored for olfactory sensory neurons, despite the analogies that are frequently made between these two systems. More attention must be paid to odorant receptor gene choice and expression during development and neuronal differentiation.