Identification of opiate receptors some 30 years ago provided tools that brought major new insights into how these drugs act and led to the discovery of a novel group of atypical neurotransmitters, the peptide enkephalins being the first. The ligand binding techniques that were used to identify opiate receptors were employed to characterize receptors for all of the major neurotransmitters in the brain leading to additional insights into the actions of many drugs, such as neuroleptics. These techniques also permitted characterization of intracellular signaling systems such as the IP3 receptor and immunophilins. Even more novel than the enkephalins have been the gaseous neurotransmitters NO and CO and D-serine. (C) 2004 Elsevier Ltd. All rights reserved.