It is only recently that a number of studies on synaptic plasticity in the hippocampus and other brain areas have considered that a heterosynaptic modulatory input could be recruited as well as the coincident firing of pre- and post-synaptic neurons. So far, the strongest evidence for such a regulation has been attributed to dopaminergic (DA) systems but other modulatory pathways have also been considered to influence synaptic plasticity. This review will focus on dopamine contribution to synaptic plasticity in different brain areas (hippocampus, striatum and prefrontal cortex) with, for each region, a few lines on the distribution of DA projections and receptors. New insights into the possible mechanisms underlying these plastic changes will be considered. The contribution of various DA systems in certain forms of learning and memory will be reviewed with recent advances supporting the hypothesis of similar cellular mechanisms underlying DA regulation of synaptic plasticity and memory processes in which the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway has a potential role. To summarize, endogenous DA, which depends on the activity patterns of DA midbrain neurons in freely moving animals, appears as a key regulator in specific synaptic changes observed at certain stages of learning and memory and of synaptic plasticity.