A large number of different types of medications are used to treat insomnia. The benzodiazepines are a group of chemically related agents that have a therapeutic effect on insomnia through enhancing the inhibitory effects of gamma-amino-butyric acid (GABA), the predominant inhibitory neurotransmitter in the brain and the most important sleep-promoting system. Available melatonin receptor agonists include melatonin and ramelteon. These agents are believed to exert their therapeutic effects on insomnia primarily through binding to MT1 and MT2 melatonin receptors. Antidepressants are frequently used to treat insomnia in clinical practice, though relatively little data exist on the treatment of insomnia patients with these agents. These agents promote sleep by antagonism of the wake-promoting systems norepinephrine, histamine, and acetylcholine. The majority of insomnia cases occur with medical and psychiatric conditions. Longstanding clinical guidelines published in 1983 discouraged targeting treatment to insomnia in those with medical and psychiatric disorders.