Seafood poisoning results from the ingestion of fish and shellfish that contain toxic substances. Patients can present with a wide range of gastrointestinal and neurological symptoms that can range in severity. Seafood-related toxins have no known antidotes. While most illnesses are usually mild and only need symptomatic treatment, there are instances in which patients can have severe symptoms, such as cardiovascular collapse, and require ventilatory support. It is important for clinicians to consider seafood poisoning in their differential diagnoses when patients present with concerns of a foodborne illness. This chapter focuses on seafood toxins that are most often ingested as well as with those that are rarely encountered but can be lethal.