Objective Shellfish toxins are not only threatening to quality of marine aquatic products but also become a potential threat to human health. As the structure diversity and function mechanism complexity，the monitoring programs of shellfish toxins using animal models are costly，difficult to quantitate and not meet 3R principles. There is a pressing need to develop new methods to reduce quantity of used animals and to relieve animal distress. Recently，many new assays based on action mechanisms have been developed including functional，immunological，chemical analysis and biosensor methods. These methods promote the efficacy of shellfish toxin monitoring，and will be accepted by administration for regulation programs provided these approaches be scientifically validated and standardized.