Kainate receptors, one of the three subtypes of ionotropic receptors for the excitatory transmitter l-glutamate, play a variety of functions in the regulation of synaptic activity. Their physiological properties and functional roles have been identified only recently, following the discovery of selective pharmacological tools that allow for isolation of kainate receptor-mediated events. A considerable amount of data indicates that this class of glutamate receptors is located both at the pre- and postsynaptic site, playing a special role in regulating transmission and controlling short- and long-term plasticity. In this review, we summarize some data obtained in our laboratory over the last decade illustrating how various ligands have contributed to our understanding of the physiological role for neuronal kainate receptors. In particular, we show that the GluK1-containing KARs are important for regulating synaptic facilitation and LTP induction at hippocampal mossy fiber synapses.