The serotonergic nervous system plays crucial roles in regulating psycho-emotional, cognitive, sensori-motor and autonomic functions. It is now known that multiple serotonin (5-hydroxytryptamine; 5-HT) receptors regulate extrapyramidal motor functions, which are implicated in pathogenesis and/or treatment of various neurological disorders ( e.g. , Parkinson’s disease and drug-induced extrapyramidal motor deficits). Specifically, antagonism of 5-HT_2A/2C receptors alleviates antipsychotic-induced extrapyramidal side effects (EPS) by relieving the 5-HT_2A/2C receptor-mediated inhibition of nigral dopaminergic neuron activity and striatal dopamine release. Indeed, many of the second generation antipsychotics ( e.g. , risperidone, perospirone and olanzapine) commonly possess potent 5-HT_2A/2C blocking actions which contribute to their atypical antipsychotic property. In addition, activation of 5-HT_1A receptors also improves antipsychotic-induced EPS and motor disabilities in animal models of Parkinson’s disease. Microinjection studies revealed that stimulation of postsynaptic 5-HT_1A receptors in the striatum or motor cortex plays an important role in the antiparkinsonian actions. Furthermore, recent studies demonstrated that antagonism of 5-HT₃ and 5-HT₆ receptors alleviates extrapyramidal motor disorders while 5-HT₄, 5-HT₅, and 5-HT₇ receptors are mostly inactive. These results encourage drug discovery research into new 5-HT receptor ligands that could improve current therapies for extrapyramidal motor disorders.