Activity-dependent changes in synaptic and neuronal efficacy are thought to be among the main events underlying the storage of information under the form of new memories. Several studies directed to uncover the molecular mechanisms responsible for the regulation of synaptic function and memory acquisition indicate that modification of the phosphorylation/activation state of different synaptic and nuclear-localized protein kinases plays a critical role in the onset and maintenance of the long-lasting potentiation of synaptic responses and the establishment of perdurable memories. Here we review some of the more recent findings concerning the regulation of these protein kinases and their participation in synaptic plasticity and mnemonic processes.