Scombroid poisoning, also called histamine fish poisoning, is an allergy-like form of food poisoning that continues to be a major problem in seafood safety. The exact role of histamine in scombroid poisoning is not straightforward. Deviations from the expected dose-response have led to the advancement of various possible mechanisms of toxicity, none of them proven. Histamine action levels are used in regulation until more is known about the mechanism of scombroid poisoning. Scombroid poisoning and histamine are correlated but complicated. Victims of scombroid poisoning respond well to antihistamines, and chemical analyses of fish implicated in scombroid poisoning generally reveal elevated levels of histamine. Scombroid poisoning is unique among the seafood toxins since it results from product mishandling rather than contamination from other trophic levels. Inadequate cooling following harvest promotes bacterial histamine production, and can result in outbreaks of scombroid poisoning. Fish with high levels of free histidine, the enzyme substrate converted to histamine by bacterial histidine decarboxylase, are those most often implicated in scombroid poisoning. Laboratory methods and screening methods for detecting histamine are available in abundance, but need to be compared and validated to harmonize testing. Successful field testing, including dockside or on-board testing needed to augment HACCP efforts will have to integrate rapid and simplified detection methods with simplified and rapid sampling and extraction. Otherwise, time-consuming sample preparation reduces the impact of gains in detection speed on the overall analysis time.