Horseshoe crabs (Limulus polyphemus and Asian species) are harvested annually for biomedical purposes - their blood contains Limulus Amebocyte Lysate (LAL), used universally to test medical devices and vaccines for bacterial endotoxin contamination. An estimated 500,000 Atlantic horseshoe crabs are bled annually in the US, with mortality rates disputed: industry claims 3-15%, independent research suggests 10-30% mortality. Surviving crabs are returned to the sea but may show reduced mobility and spawning behaviour. Recombinant Factor C (rFC) technology offers a synthetic alternative to LAL validated for most applications, eliminating horseshoe crab bleeding. European Pharmacopoeia approved rFC in 2020; US FDA is evaluating. Horseshoe crabs are also harvested as bait for eel and conch fishing, further stressing populations important for migratory shorebird food chains. The welfare status of horseshoe crabs is uncertain given their simple neural architecture, but precautionary concern is warranted given their ecological importance.