Blood from horseshoe crabs is essential for many drug, implant and environmental safety tests—but blood harvesting, together with capture for bait and impacts from climate change and habitat destruction, is threatening populations of these “living fossils.” A review published in Frontiers in Marine Science highlights that these continuing threats will detrimentally affect the surrounding ecosystem, including migratory shorebirds who rely on horseshoe crab eggs for food. To enable a sustainable harvest of their blood for the biomedical industry —which currently is entirely dependent on these creatures for drug and environmental safety testing—alternative tests should be explored in conjunction with better harvesting and conservation strategies.