Description: Naturally occurring neurotoxins belonging to two structurally distinct groups of guanidinium alkaloids known collectively as saxitoxins (STXs) and tetrodotoxins (TTXs) share a high affinity and ion flux blockage capacity for voltage-gated sodium ion channels (NaV). Both toxin groups are produced by marine microorganisms and widely distributed among vector species in the oceans, but are also found in terrestrial species. The STXs are often referred to as paralytic shellfish toxins (PSTs) based on their accumulation in shellfish and the symptoms in humans after consumption of toxic seafood. Biosynthesis of STXs is confirmed in four genera of marine dinoflagellates and among about a dozen species of primarily freshwater and brackish water strains of filamentous cyanobacteria. The origin of the STX biosynthetic genes in dinoflagellates remains controversial and may represent multiple horizontal gene transfer (HGT) events from progenitor bacteria and/or cyanobacteria. The recent identification of the biosynthetic genes for STX analogs in both cyanobacteria and dinoflagellates has yielded insights into mechanisms of toxin heterogeneity among species and the evolutionary origins of the respective elements of the toxin gene cluster. The biogenic origins of TTXs and tetrodotoxicity remain even more enigmatic. The TTXs occur primarily in marine pufferfish species, and hence tetrodotoxicity is frequently described as pufferfish poisoning (PFP) after the toxin syndrome in human consumers of such toxic fish. In marine environments, TTXs also appear in invertebrate species, particularly of benthic feeders on suspended particulates and carnivorous vector species. Symbiotic colonizing bacteria or free-living bacteria sequestered via feeding from the water column or sediments are most often invoked as proximal sources of TTXs in marine macrofauna, but endogenous biosynthesis independent of bacteria cannot be excluded. The TTX biosynthetic pathway has not been completely elucidated, and the biosynthetic genes are unknown.