In the case of sea lamprey control in the Great Lakes, anecdotal evidence from regulators, scientists, representatives of advocacy groups, and members of Indigenous communities suggests that a good deal of skepticism and opposition to existing control methods (including those that involve chemicals as well as barriers) is present within Indigenous communities, and that this may pose a serious challenge to sea lamprey control efforts in the near and long terms. The social acceptability of control efforts depends on the support of key communities––in other words, control efforts require “social license” built on trust and confidence in scientists and regulators and their actions. Social science research to understand Indigenous perspectives (including the range of perspectives and their grounding in knowledge and values), coupled with Indigenous methodologies, would inform ongoing communication and the public engagement activities needed to maintain the social license to deliver the sea lamprey control program.