Recent studies have provided new insights into the role of presynaptic ligand-gated ion channels in modifying synaptic transmission. Along with a growing list of different types of presynaptic ionotropic receptors and the cell types that express them, there have been advances in characterizing the molecular components of the receptors as well as the signaling processes that link receptor activation to changes in neurotransmitter release. Perhaps most striking is the recent convergence of data from biochemical, molecular and electrophysiological studies, implicating presynaptic ionotropic receptors in the effects of psychoactive and addictive drugs.