The relay nuclei of the auditory brainstem contain some of the largest nerve terminals in the mammalian brain. Endbulb and calyceal synapses convey signals with a high degree of precision and reliability. However, recent studies reveal that these synapses possess numerous and remarkably diverse mechanisms for the modulation of transmitter release. The implication is that successful relay of signals in vivo may require the ability to fine-tune synaptic transmission.