Groupers are a valuable fishery resource of reef ecosystems and are among those species most vulnerable to fishing pressure because of life history characteristics including longevity, late sexual maturation and aggregation spawning. Despite their economic importance, few grouper fisheries are regularly monitored or managed at the species level, and many are reported to be undergoing declines. To identify major threats to groupers, the International Union for Conservation of Nature (IUCN) Red List criteria were applied to all 163 species. Red List assessments show that 20 species (12%) risk extinction if current trends continue, and an additional 22 species (13%) are considered to be Near Threatened. The Caribbean Sea, coastal Brazil and Southeast Asia contain a disproportionate number of Threatened species, while numerous poorly documented and Near Threatened species occur in many regions. In all, 30% of all species are considered to be Data Deficient. Given that the major threat is overfishing, accompanied by a general absence and/or poor application of fishery management, the prognosis for restoration and successful conservation of Threatened species is poor. We believe that few refuges remain for recovery and that key biological processes (e.g. spawning aggregations) continue to be compromised by uncontrolled fishing. Mariculture, through hatchery-rearing, increases production of a few species and contributes to satisfying high market demand, but many such operations depend heavily on wild-caught juveniles with resultant growth and recruitment overfishing. Better management of fishing and other conservation efforts are urgently needed, and we provide examples of possible actions and constraints.