Border regions are not often associated with innovation and economic prosperity. And even when they are prosperous, cross-border interaction is still mostly limited. The opening up of borders in Europe has presented new opportunities for firms located in these border regions to co-operate for innovation and knowledge to flow across borders. Despite the reduction of the importance of borders, firms seeking to access cross-border knowledge resources need still to ‘cross’ the border and address the various effects it brings. This paper therefore asks the question of how the presence of a border affects the processes by which firms attempt to build up productive co-operations for innovation. We use a heuristic of collaborative innovation across borders as building up through four sequential cooperation stages, and each of these different stages is susceptible to different kinds of border effects. Using a case study of firms co-operating across the Dutch-Flemish border, we empirically explore these border crossing processes in order to shed further light on how border processes play out.