The impact of global activism against trade liberalisation is examined in this article through an analysis of the initiatives of cross border civil society networks and with a particular attention to the failed 2003 WTO Ministerial Conference in Cancun. Key aspects considered here include the internal dynamics of mobilisation – which was characterised by a strong framing and widespread protest - and the political opportunities in WTO negotiations, which were marked by divisions within the North and resistance by a large group of Southern governments. In the failure of the WTO Millennium Round in Cancun and the loss of momentum of its liberalisation agenda, a significant role has been played by civil society activism and its ability to combine protest, well-prepared lobbying, an epistemic-like community able to influece public opinion, and the development of alliances with like-minded governments of the South.