Chemical neuroecology examines the relationships between chemosensory physiology, behavior, and population and community dynamics. A keystone species, for example, is one whose impact on communities is far greater than would be predicted from its relative abundance and biomass. Neurotoxins, then, could function in keystone roles. Rare within natural habitats, they exert strong effects on species interactions at multiple trophic levels. Effects of two guanidine alkaloids, tetrodotoxin (TTX) and saxitoxin (STX), coalesce neurobiological and ecological perspectives. These potent neurotoxins function as chemical defenses by binding to voltage-gated sodium channels on nerve and muscle cells. When borrowed by resistant consumer species, however, they are used in chemical defense against higher-order predators or as chemosensory excitants in mediating critical behavioral interactions. Through a combination of diverse physiological traits, TTX and STX exert profound impacts reverberating across multiple trophic levels and determining a wide range of community-wide attributes. Such traits ultimately render TTX and STX fully functional as keystone molecules, with vast ecological consequences for species assemblages and rates of material exchange.