Dopamine exerts important effects on its target neurons by modulating their responses and by altering synaptic plasticity. These functions of dopamine account for its role in different human conditions, including Parkinson disease, drug addiction, compulsive behavior, attention-deficit/hyperactivity disorder, and schizophrenia. Although diverse, these diseases correspond to, or include, alterations of the same basic neuronal processing mechanisms that are normally controlled by dopamine. Depending on the type of alterations and the predominant anatomical sites of dysfunction, the clinical manifestations are different and do not necessarily respect the traditional boundaries between neurology and psychiatry. Until recently, virtually all the drugs available to neurologists or psychiatrists were acting at the level of the neuronal membranes, modifying neurotransmitters' metabolism or interactions with receptors. Understanding the intracellular signaling pathways underlying the action of neurotransmitters, especially dopamine, suggests a new class of potential therapeutic agents that could target a specific protein kinase or a phosphatase. In principle, one advantage of pharmacological manipulation of signaling pathways is that it would not alter basic function but only modify regulatory processes. For example, inhibitors of protein kinases modulating DARPP-32 could have applications in enhancing or decreasing specific aspects of dopamine actions. Knowledge of the signaling pathways activated by dopamine also allows us to look for changes in these pathways in pathologic conditions. At present, this approach is limited in humans to the search for mutations in the genes of the relevant proteins and for variation of their levels in postmortem brain samples. Therefore, it will be challenging to design novel methods allowing the study of intracellular signaling pathways in vivo by noninvasive approaches. The use of experimental animal models and the design of drugs capable of selectively altering these pathways should allow important progress to be made.