Domoic acid (DA), a neurotoxic amino acid produced by some strains of phytoplankton, is responsible for the human toxic syndrome amnesic shellfish poisoning. This exocitotoxin results in neuronal degeneration and necrosis in specific regions of the hippocampus. Because DA accumulates mostly in shellfish, causing outbreaks in different countries, screening for DA has been carried out with various assays. Although bioassays and immunoassays have been developed, several liquid chromatographic methods for the determination of DA in different matrices such as shellfish, algae, or seawater have been reported. Additionally, other alternative methods such as capillary electrophoresis and capillary electrochromatography have been described. This paper summaries the toxicology, the chemistry, and the developed determination methods of DA.