Venkataramanujam Srinivasan,1 Domenico De Berardis,2,3 Timo Partonen,4 Rahimah Zakaria,5 Zahiruddin Othman6 1Sri Sathya Sai Medical Educational and Research Foundation, Coimbatore, India; 2Psychiatric Service of Diagnosis and Treatment, Giuseppe Mazzini Hospital, Teramo, 3Department of Neuroscience and Imaging, Gabriele d'Annunzio University, Chieti, Italy; 4Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland; 5Department of Physiology, 6Department of Psychiatry, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia Abstract: Most patients with Parkinson's disease (PD) experience sleep-related problems, such as difficulty in initiating and maintaining sleep, excessive daytime sleepiness, sleep fragmentation, reductions in non-rapid eye movement (NREM) or rapid eye movement (REM) sleep, and REM sleep behavior disorder. Although motor symptoms of PD are treated with dopaminergic drugs, the nonmotor symptoms pose a big problem, and they often precede the onset of the disease. Treating the nonmotor symptoms, such as sleep and associated behavioral disorders, is beneficial, for it not only relieves the symptoms but also helps to slow the progression of the disease. Treating PD patients with melatonin has been shown to be beneficial in treating sleep and behavior problems. The finding of reduced expression of the MT1 and MT2 melatonin receptors in amygdalae and substantia nigra of PD patients supports the involvement of melatonergic system in the etiology of PD. Hence, the use of melatonin or its analogs may even be beneficial not only for improving sleep quality but also for enhancing neuroprotection in PD. Keywords: REM sleep-behavior disorder, insomnia, melatonin receptors, circadian dysregulation