The twentieth anniversary of the United Nations Convention against Transnational Organized Crime (Palermo, 2000) is a timely moment for an appraisal of the Convention system, its developments (including the recently adopted review mechanism) and the challenges it faces. In The Palermo Convention at Twenty: Institutional and Substantive Challenges experts with different backgrounds begin such a discussion by focusing on the institutional and substantive features of the Convention and its potential as a tool for countering different forms of criminality – including some that were not meant, in principle, to fall under its scope.