Giant clams are considered iconic coral reef megafauna and one of the Great Barrier Reef’s “Great 8” animals. Giant clams are the world’s largest bivalve molluscs, with long generation times; however, they are threatened by overexploitation for human consumption, their valuable shells and the aquarium trade. Consequently, giant clams are now extinct in some former areas of their global range, are included in the IUCN Red List of Threatened Species and are CITES-listed. Now, giant clams are threatened additionally by rapid environmental change from both global change stressors, including ocean warming and acidification, and local- to regional-scale stressors, such as declining water quality and pollution. The true giant clam was uplisted to Critically Endangered on the IUCN Red List in 2024. This presentation will show how multiple global- to local-scale stressors are likely to cause an array of effects on survival, growth and performance, potentially limiting giant clam depth distribution on coral reefs and decreasing suitable habitat area. Further work on how global change responses translate into habitat requirements, selective breeding for resilience, the capacity for rapid adaptive responses of the holobiont, and enhancing wildlife tourism potential may help improve the prospects of these key, iconic species over coming decades.