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The mega-regional trade agreements, particularly the Trans-Pacific Partnership, the Transatlantic Trade and Investment Partnership, and the Trade in Services Agreement, represent a new phenomenon for the global trading system. As major preferential trade agreements that involve the world’s largest economies (the United States and the European Union), they cover a large share of global trade and, thus, generate large spillover effects on non-parties to the negotiations. Further, the ambitious rule-making agenda shifts the locus of global rule-making and standard-setting from the inclusive World Trade Organization to the small number of participants in these negotiations. These rules and standards will shape markets and, thus, amplify the direct effect of discriminatory preferences. This article discusses the factors driving the mega-regionals, considers the significance of these negotiations for excluded parties, and suggests how India, in particular, might respond.