This is a critical review of the global distribution, sources of variation in toxicity, anatomical partitioning, metabolism, and detoxification kinetics of paralytic shellfish poisoning (PSP) toxins (carbamate, TV-sulfocarbamoyl, and decarbamoyl saxitoxin derivatives) in bivalve molluscs. Marked interspecific differences in toxin accumulation are related to differences in toxin sensitivity, determined from neurological, physiological, and behavioral responses. Toxicity also varies considerably with body size, immersion time, off-bottom position, and over distances ≤1 km. Bivalve species can be broadly classified as rapid (e.g.,Mytilus eduJis) or slow detoxifiers (e.g.,Placopecten mageJJanicus). The former takes weeks to detoxify to the regulatory level (up to 15% toxin loss day−1); the latter takes months to years to detoxify (≤3% loss day−1). Toxin biotransformation, which may lead to changes in net toxicity, varies greatly among species. A few clam species, such asProtothaca stamineaandSpisula solidissima, exhibit rapid enzymatic decarbamoylation, whereas other bivalves (e.g.,Mya arenariaandM. edulis) show limited toxin metabolism and thus are useful indicators of the toxigenic source. Pronounced changes in toxin composition occur when algae are rich in low-potency,N-sulfocarbamoyl toxins. Analysis of toxin composition and relative toxin levels of viscera and other tissues can be used to predict the timing of toxic blooms. This review highlights information required to select aquaculture species and effectively manage stocks in PSP-affected areas. Caveats in the interpretation of existing data and needs for future research are identified.