Seafood poisoning has been recognized as a problem in both coastal and inland populations for millennia. Many types of sea creatures from shellfish to the largest fish have been implicated. Severe cases of many different types of seafood poisonings can result in fatalities. While the pathophysiology of the toxins is well known in some cases, others, like ciguatera, remain somewhat confusing. As a result, the treatment of these conditions remains controversial, although supportive care continues to be the mainstay of therapy. In this manuscript, we review the pathophysiology, clinical presentation, and treatment of some of the most common and toxic varieties of seafood poisoning resulting from toxins.