The design and fabrication of 2D nano-porous architectures with controllable porosity and pore structure, as well as unique properties at the nanoscale are critical for applications such as separation, sensing, energy and catalysis. Perforation strategies across 2D materials, primarily graphene, have shown promising opportunities to develop nanostructures with tunable ranges of pore size distribution, pore density and uniformity. In addition, the perforated graphene structures exhibit improved properties in terms of plasmonic diffusion, catalytic activity and thermo-electrical properties compared to dense 2D materials and are opening new avenues for the development of responsive or reactive materials. This review presents and discusses the very recent developments in the synthesis of perforated graphene-based materials and correlates the morphology and other properties of such 2D nano-porous materials to their performance in applications such as separation, sensing and energy. Challenges related to the controlled engineering and manufacturing of such nanostructures particularly from a scalability point of view, as well as potential avenues for performance improvements through alternative 2D perforated materials are also critically evaluated.