Each May, red knots (Calidris canutus rufa) congregate in Delaware Bay during their northward migration to feed on horseshoe crab eggs (Limulus polyphemus) and refuel for breeding in the Arctic. During the 1990s, the Delaware Bay harvest of horseshoe crabs for bait increased 10-fold, leading to a more than 90% decline in the availability of their eggs for knots. The proportion of knots achieving weights of more than 180 grams by 26–28 May, their main departure period, dropped from 0.6–0.8 to 0.14–0.4 over 1997–2007. During the same period, the red knot population stopping in Delaware Bay declined by more than 75%, in part because the annual survival rate of adult knots wintering in Tierra del Fuego declined. Despite restrictions, the 2007 horseshoe crab harvest was still greater than the 1990 harvest, and no recovery of knots was detectable. We propose an adaptive management strategy with recovery goals and annual monitoring that, if adopted, will both allow red knot and horseshoe crab populations to recover and permit a sustainable harvest of horseshoe crabs.