Harmful algal blooms (HABs) can produce biotoxins that accumulate in seafood species targeted by commercial, recreational, and subsistence fisheries and pose an increasing risk to public health as well as fisher livelihoods, recreational opportunities, and food security. Designing biotoxin monitoring and management programs that protect public health with minimal impacts to the fishing communities that underpin coastal livelihoods and food systems is critically important, especially in regions with worsening HABs due to climate change. This study reviews the history of domoic acid monitoring and management in the highly lucrative U.S. West Coast Dungeness crab fishery and highlights three changes made to these programs that efficiently and adaptively manage mounting HAB risk: (1) expanded spatial-temporal frequency of monitoring; (2) delineation of clear management zones; and (3) authorization of evisceration orders as a strategy to mitigate economic impacts. Simulation models grounded in historical data were used to measure the value of monitoring information in facilitating efficient domoic acid management. Power analysis confirmed that surveys sampling 6 crabs (the current protocol) have high power to correctly diagnose contamination levels and recommend appropriate management actions. Across a range of contamination scenarios, increasing the spatial-temporal frequency of monitoring allowed management to respond more quickly to changing toxin levels and to protect public health with the least impact on fishing opportunities. These results highlight the powerful yet underutilized role of simulation testing and power analysis in designing efficient biotoxin monitoring programs, demonstrating the credibility of these programs to stakeholders, and justifying their expense to policymakers.