Ionotropic neurotransmitter receptors mediate rapid synaptic transmission in the CNS and PNS. Owing to this central role in trans-synaptic signal transduction, modulation of these receptors could play a crucial role in the expression of synaptic plasticity in the brain. AMPA receptors mediate the majority of rapid excitatory synaptic transmission in the CNS. Recent studies have indicated that the activity and synaptic distribution of these receptors is dynamically regulated and could be crucial for the short- and long-term modification of synaptic efficacy. Here we review recent data on the molecular mechanisms that underlie the modulation of AMPA receptors and the role of AMPA-receptor regulation in mediating synaptic plasticity.