Preventing and addressing research misconduct demands more than imploring scientists to do better. It is also essential to address the structural issues that allow misconduct to flourish. With these structural factors in mind, this Special Issue explores the institutional obligations of journals and publishers, research institutions, funders, and the government to promote scientific integrity and advance trust in science. Articles from researchers affected by fraud, science “sleuths,” systematic reviewers, journal editors, academic officials, regulators, and leading experts on research integrity offer a range of ideas for responding to the research misconduct crisis, including increased transparency, stronger journal processes for review and retraction, improved scientific lab culture, and efforts to hold investigators prospectively accountable for scientific integrity, among several others.