The Arctic cryosphere is collapsing, posing overlapping environmental risks. In particular, thawing permafrost threatens to release biological, chemical and radioactive materials that have been sequestered for tens to hundreds of thousands of years. As these constituents re-enter the environment, they have the potential to disrupt ecosystem function, reduce the populations of unique Arctic wildlife and endanger human health. Here, we review the current state of the science to identify potential hazards currently frozen in Arctic permafrost. We also consider the cascading natural and anthropogenic processes that may compound the impacts of these risks, as it is unclear whether the highly adapted Arctic ecosystems have the resilience to withstand new stresses. We conclude by recommending research priorities to address these underappreciated risks.