The nicotinic acetylcholine receptor has served, since its biochemical identification in the 1970's, as a model of allosteric ligand-gated ion channel mediating signal transition at the synapse. In recent years, the application of X-ray crystallography and high-resolution cryo-electron microscopy together with molecular dynamic simulations to nicotinic receptors and homologs have opened a new era in the understanding of channel gating by the neurotransmitter. They reveal, at atomic resolution, the diversity and flexibility of the multiple ligand-binding sites including recently discovered allosteric modulatory sites distinct from the neurotransmitter orthosteric site and the conformational dynamics of the activation process as a molecular switch linking together these multiple sites. The model emerging from these studies paves the way to a new pharmacology based, first, upon the occurrence of an original mode of indirect allosteric modulation, distinct from a steric competition for a single and rigid binding site and, second, the design of drugs specifically interacting with privileged conformations of the receptor such as agonists, antagonists and desensitizers. The research on nicotinic receptor is still at the forefront in understanding the mode of action of drugs on the nervous system.