The serotonin 5-HT1Areceptor has attracted wide attention as a target for treatment of psychiatric disorders. Althoughthis receptor is important in the pharmacological mechanisms of action of new-generation antipsychotics, itscharacterization remains incomplete. Studies based on in vitro molecular imaging on brain tissue by autoradiography,and more recently in vivo PET imaging, have not yielded clear results, in particular due to the limitations of current 5-HT1Aradiotracers, which lack specificity and/or bind to all 5-HT1Areceptors, regardless of their functional status. Thenew concept of PET neuroimaging of functionally active G-protein-coupled receptors makes it possible to revisit PETbrain exploration by enabling new research paradigms. For the 5-HT1Areceptor it is now possible to use [18F]-F13640, a5-HT1Areceptor radioligand with high efficacy agonist properties, to specifically visualize and quantify functionallyactive receptors, and to relate this information to subjects’pathophysiological or pharmacological state. We thereforepropose imaging protocols to follow changes in the pattern of functional 5-HT1Areceptors in relation to mood deficitsor cognitive processes. This could allow improved discrimination of different schizophrenia phenotypes and greaterunderstanding of the basis of therapeutic responses to antipsychotic drugs. Finally, as well as targeting functionallyactive receptors to gain insights into the role of 5-HT1Areceptors, the concept can also be extended to the study ofother receptors involved in the pathophysiology or therapy of psychiatric disorders