This special issue focuses on the difficulties of negotiating the Transatlantic Trade and Investment Partnership (TTIP), with contributions by scholars from different perspectives. This introductory article briefly examines the trend to mega-FTAs of which TTIP is a leading example. It then reviews the contributions to this special issue, drawing on an analytical approach that reflects extant work on transnational and transgovernmental relations. This approach, we contend, helps to understand the stark mismatch between the desire of some parties to negotiate binding trade rules on behind-the-border regulatory policies in certain key sectors of national economies and the progress made in TTIP talks. We then highlight the significance of some key actors in a case study of failed E.U. attempts to include financial sector reforms and associated regulatory processes in TTIP.