In taking on the controversial debate over the role of state attorneys general in antitrust enforcement, the article draws upon recent legal and historical scholarship on federalism to argue that globalization requires a paradigm change in concepts of U.S. federalism. While many assume that increasing international economic integration makes state participation in economic regulation with international implications inherently problematic, the article demonstrates that, to the contrary, states have an important role to play in the regulation of international business. States have a long history of challenging the federal government in a way that has promoted a robust national dialogue on matters of public policy. In addition, states have historically played and should continue to play a vital role in safeguarding the health, safety, and welfare of the American public. Historical research reveals that the view of state governments as protectors of the public interest formed an important part of the Founders’ vision. Globalization may suggest that states are not capable of carrying out this function independently of the federal government. But the fact that today’s “local” threats to state residents now often spring from international sources does not suggest that states should renounce their traditional role as guardians of the public welfare. Indeed, it makes that role all the more important.