An overview is given of the different approaches that have been used to identify toxins responsible for seafood poisoning incidents, to investigate the origins of toxins, and to monitor seafood on a routine basis. It is shown that advancements in our knowledge of toxins and our ability to protect the public have often followed key developments in separation and analysis technologies. Specific examples of research in this field are presented to illustrate the significant role that chromatographic methods play. The presentation will be given in an order that reflects the typical sequence of investigations that follow a new toxin episode.