G-Protein-coupled receptors mediate many of the hypnotic and analgesic actions of the drugs employed in anesthesia. Notably, opioid agonists represent the most successful and efficacious class of analgesic agents employed over the last century. Also, major clinical advances have been made by the study of alpha(2) adrenoceptor agonists, which possess both hypnotic and analgesic qualities that are being increasingly exploited in both anesthetic and critical care settings. Furthermore orexin, gamma-aminobutyric acid (GABA) (B), and muscarinic cholinergic receptors have been identified as potential anesthetic targets; clinical exploitation of ligands at these receptors may lead to important advances in anesthetic pharmacology. In this review we discuss the relevant molecular and neural network pharmacology of anesthetic agents acting at G-protein-coupled receptors.