The role of desensitization of ligand-gated channels at fast chemical synapses has been difficult to establish. Densensitization has been studied traditionally with prolonged agonist exposure, whereas the duration of free neurotransmitter in the synaptic cleft is relatively brief. Studies of acetylcholine-, glutamate- and GABA-gated channels using rapid agonist application now provide a means to assess the effects of densensitization in shaping synaptic responses and in influencing neuronal excitability. These data reveal several strikingly different patterns by which the receptor-specific kinetics of densensitization can determine the size, timecourse and frequency of transmitted signals. Densensitization is thus a surprisingly versatile mechanism for shaping synaptic transmission.