The excitatory amino acid domoic acid is a naturally occurring potent excitotoxin produced by various marine algae and diatoms. The toxin and its isomers are responsible for a human illness known as amnesic Shellfish poisoning. This chapter presents the chemistry, pharmacology, and toxicology of domoic acid, and reviews the main characteristics of excitatory neurotransmission, the interaction of domoic acid with glutamate receptors, and the pharmacology of domoic acid and its isomers. -Glutamate mediates the majority of excitatory neurotransmission in the brain and spinal cord, and recent evidence suggests that glutamatergic receptors are also expressed by immune cells, regulating the degree of cell activation. The ionotropic class of glutamate receptors are integral membrane proteins composed of several subunits that assemble to form a central ion channel pore. Amino-3-hydroxy-5-methylisoxazoleproprionic acid receptors are one type of ionotropic glutamate receptors involved in rapid excitatory synaptic transmission.