Among the characterized dopamine receptor subtypes, $D_2$ receptor ($D_2R$) and $D_3$ receptor ($D_3R$) are the main targets of neuroleptics that are currently in use. In particular, $D_3R$ is closely related to the etiology of schizophrenia and drug addiction. The spatial expression patterns of $D_2R$ and $D_3R$ are distinct in certain areas of the brain. $D_2R$ are heavily expressed in the regions responsible for motor functions, whereas $D_3R$ are more selectively expressed in the limbic regions, which are associated with cognitive and emotional functions. Therefore, disturbances in the motor and endocrine functions, which are the most serious problems caused by the current neuroleptics, are likely to result from the non-selective blockade of $D_2R$. Selective regulation of $D_3R$ is needed to separate the desired therapeutic activities from unwanted side effects that result from promiscuous blockade of other receptors. $D_2R$ and $D_3R$ possess high sequence homology and employ similar signaling pathways, and it is difficult to selectively regulate them. In this review, we discuss the signaling mechanisms, intracellular trafficking, and desensitization properties of $D_2R$ and $D_3R$. In addition, the proteins interacting with $D_2R$ or $D_3R$ are discussed in relation to their roles in the regulation of receptor functions, followed by the current status of the development of selective $D_3R$ ligands.