REM sleep behavior disorder (RBD) is characterized by complex behavioral manifestations in response to dream content that may cause sleep disruption or injuries to the patient or the bed partner. In this case, the patients need treatment to control their symptoms. Pharmacologic agents have been reported to have positive and negative impacts on REM sleep muscle atonia and the motor behaviors associated with RBD. Clonazepam is efficacious and well tolerated by the majority of patients afflicted by RBD and should be considered as initial treatment. In patients at risk of falls who have cognitive impairment or who have obstructive sleep apneas, melatonin may be a good alternative to clonazepam. Anticholinesterase inhibitors and dopaminergic agents are not of clear benefit. Monoamine oxidase inhibitors, tricyclic antidepressants, serotonergic synaptic reuptake inhibitors, and noradrenergic antagonists can induce or aggravate RBD symptoms and should be avoided in patients with RBD. When these agents are prescribed to patients with neurodegenerative disorders or narcolepsy who are at risk of developing RBD, systematic follow-up may be warranted to detect the emergence of RBD symptoms.