REM Sleep Behavior Disorder (RBD) is commonly associated with neurodegenerative diseases and leads to abnormal and often aggressive behavior during sleep, often causing injury to selfor the bed partner. Clonazepam and melatonin have been considered as treatments of RBD, but the underlying mechanism of action is unknown. Melatonin may restore the presence of physiological REM sleep muscle atonia. A clinical protocol was established to follow patients with RBD with clinical evaluation and polysomnography (PSG). A retrospective analysis was then performed on data from 28 RBD patients. From the obtained data, melatonin 6 mg has a positive effect on both clinical manifestation and PSG findings. Most subjects responded to melatonin 6 mg with a significant decrease or absence of abnormal behavior, and less than 20% of EMG bursts during total REM time during PSG, but one patient never responded to the drug even at up to 12 mg of melatonin and 3 mg of clonazepam. Depending on the patient, more disturbed sleep was noted with melatonin alone than with he combination of both melatonin and clonazepam, and a further decrease of “wake after sleep onset” was noted at polysomnography.