This chapter discusses the politics of the La Plata River Basin to reflect on the prospects of creating regional frameworks of transboundary basin governance. It explores the emerging conflicts and agendas associated with resource-driven integration which points to the political challenges ahead that states and societies need to tackle to advance in the creation of a transboundary basin governance framework for the La Plata River Basin. The dynamics of conflict and cooperation over transboundary waters is at the centre of the origins of regionalism in the Southern Cone countries of South America. The chapter shows that the structural constraints on region-building introduced by an underlying logic of fragmentation and competition between states and actors in the basin. Resource-based competition in international markets is conducive to uncooperative logics with the resulting outcome of depletion of natural resources and related socio-environmental conflicts.