In the cerebral cortex and the hippocampus, excitatory synaptic neurotransmission is mediated mainly by glutamatergic synapses. These synapses undergo changes in strength depending upon paired presynaptic and postsynaptic activity in the same general way that had been predicted to underlie associative learning. Furthermore, activity-dependent formation and elimination of these synapses has been hypothesized to be a substrate for long-term synaptic plasticity, which may underlie long-term memory. Clearly, better understanding of the factors determining the strength of glutamatergic transmission, the plasticity of its strength, and the formation/elimination of glutamatergic synapses will bring us closer to understanding the cellular basis of learning and memory.