Serotonin (5-hydroxytryptamine) is an important biogenic amine that fulfills the role of neurotransmitter and neuromodulator. It has been a focus of interest during the last decade. Its diversity of pharmacologic actions is related to a wide variety of receptors and effector mechanisms. Seven serotonin receptor families have been identified thus far. They are genetically different transmembrane proteins composed of several hundred amino acids. The majority of these are G-protein-coupled, except the 5-HT3 receptors, which are directly ligand gated to fast ion channels. Serotonin is widely distributed in the body within the central and peripheral nervous systems, smooth muscles, and platelets, in particular. Consequently, its effects manifest mainly in these organs and influence a wide variety of neural, vascular, smooth muscle, and platelet functions. (Melatonin, a physiologically active metabolite of serotonin, is also instrumental in affecting many neural and hormonal functions.) Several selective agonists and particularly many selective antagonists have been developed for serotonin, which helped the serotonin receptor subtype classification. Some of these drugs are also used therapeutically in the treatment of migraine (eg, sumatriptan, which is a 5-HT1 receptor agonist), vascular disorders (5-HT2 antagonists), and nausea and vomiting (5-HT3 antagonists, eg, dolasetron, granisetron, ondansetron, and tropisetron), and have been investigated in gastrointestinal motility disorders (5-HT4 antagonists) and behavioral psychopathologies (5-HT1 agonists and 5-HT2-4 antagonists). Serotonin reuptake inhibitors are of particular clinical importance in the treatment of psychological illness. Future use of these drugs is also envisioned in the treatment of certain types of pain syndromes. Awareness of the serotonergic drugs and the recognition of possible drug interactions among drugs that influence serotonergic mechanisms in humans are becoming increasingly important in the practice of anesthesiology.