Hypoxia is a mounting problem affecting the world's coastal waters, with severe consequences for marine life, including death and catastrophic changes. Hypoxia is forecast to increase owing to the combined effects of the continued spread of coastal eutrophication and global warming. A broad comparative analysis across a range of contrasting marine benthic organisms showed that hypoxia thresholds vary greatly across marine benthic organisms and that the conventional definition of 2 mg O2/liter to designate waters as hypoxic is below the empirical sublethal and lethal O2 thresholds for half of the species tested. The effects of the presence of sulfide and warming were also tested to assess the responses of benthic organisms to hypoxia and these environmental stressors. Both environmental factors showed a negative impact on survival of marine benthic communities under hypoxia and suggest that the threats derived from hypoxia to marine biodiversity are greater than anticipated on the basis of the direct effects of low oxygen concentration alone. These results imply that the number and area of coastal ecosystems affected by hypoxia and the future extent of hypoxia impacts on marine life have been generally underestimated.