Since its inception the U.S. Fish and Wildlife Service’s Aquatic Animal Drug Approval Partnership Program (AADAP) has played a role in the FDA approval of almost all of the currently approved aquaculture drugs. Despite these successes, there are still currently no approved drugs for use on marine finfish. With the significant potential for mariculture expansion in the U.S. and the renewed commitment to the support of marine aquaculture by federal agencies, it is imperative to stock marine aquaculture’s medicine chest. In the past few years, AADAP has increased our efforts to help secure the first aquatic animal drug approval in saltwater in the U.S. With the help of our partners, we have made progress on saltwater finfish claims for AQUI-S 20E, Aquaflor, and 35% Perox-Aid. There are currently several challenges with saltwater drug approvals that do not exist for freshwater approvals, since the paradigm of what is required by FDA has not been fully established. This is further complicated by the small scale of the U.S. marine aquaculture industry, which creates a lot of uncertainty in the current and future use patterns of each drug in marine aquaculture. This presentation will summarize the successes, failures, obstacles, challenges, and opportunities for advancing marine aquaculture drug approvals, and outline ways to make the process as efficient as possible by utilizing the lessons learned through decades seeking aquaculture drug approvals in freshwater.