This paper provides a comparative history of radical pan-Americanism with the view to examining its potential under contemporary geo-political and socio-economic conditions. Radical pan-Americanism has manifested itself in different ways according to specific national contexts and historical circumstances. It has been inspired by local popular struggles against imperialist power and through the recognition of a shared history. In contrast, hegemonic pan-Americanism has tended to be driven by the interests of powerful states and their strategic interests. We emphasise how radical pan- Americanism has periodically reappeared in response to the prevailing form of hegemonic pan-Americanism. Two historical traditions are examined—the Venezuelan tradition and the Nicaraguan tradition. These examples suggest that the possibilities of uniting local inflections of radical pan-Americanism depend upon the prevailing geo-political climate. We conclude by assessing whether the early twenty-first century is a propitious moment for radical pan-Americanism, or another false dawn.