Glutamic acid functions as the major excitatory amino acid transmitter in the central nervous system. Glutamic acid receptors are implicated in a number of physiological and pathophysiological mechanisms, and much pharmacological and therapeutic interest is focused on these receptors. Fast excitatory neurotransmission is mediated through ionotropic glutamic acid receptors, of which NMDA and AMPA receptors are the best characterized. A number of selective ligands for both of these receptor types have been synthesized. The naturally occurring excitatory amino acid, ibotenic acid, has been an important lead structure in this work, involving design of conformationally restricted analogues and heterocyclic analogues, bioisosteric groups and resolution of chiral compounds. The development of potent and highly selective agonists and antagonists have shed light on the structural requirements for activation and blockade of these receptors. The principle of functional partial agonism is demonstrated in vitro using full agonists and competitive antagonists at AMPA and NMDA receptors.