Dopamine regulates movement, motivation, reward, and learning and is implicated in numerous neuropsychiatric and neurological disorders. The action of dopamine is mediated by a family of seven-transmembrane G protein-coupled receptors encoded by at least five dopamine receptor genes (D1, D2, D3, D4, and D5), some of which are major molecular targets for diverse neuropsychiatric medications. Dopamine receptors are present throughout the soma and dendrites of the neuron, but accumulating ultrastructural and biochemical evidence indicates that they are concentrated in dendritic spines, where most of the glutamatergic synapses are established. By modulating local channels, receptors, and signaling modules in spines, this unique population of postsynaptic receptors is strategically positioned to control the excitability and synaptic properties of spines and mediate both the tonic and phasic aspects of dopaminergic signaling with remarkable precision and versatility. The molecular mechanisms that underlie the trafficking, targeting, anchorage, and signaling of dopamine receptors in spines are, however, largely unknown. The present commentary focuses on this important subpopulation of postsynaptic dopamine receptors with emphases on recent molecular, biochemical, pharmacological, ultrastructural, and physiological studies that provide new insights about their regulatory mechanisms and unique roles in dopamine signaling.