Two-dimensional (2D) materials such as graphene and molybdenum disulfide have been demonstrated with a wide range of applications in electronic devices, chemical catalysis, single-molecule detection, and energy conversion. In the 2D materials, nanopores can be created, and the 2D nanoporous membranes possess many unique properties such as ultrathin thickness, high surface area, and excellent particle sieving capability, showing extraordinary promise in plenty of applications, such as sea water desalination, gas separation, and DNA sequencing. The performances of these membranes are mainly determined by the nanopore size, structure, and density, which, in turn, rely on the fabrication techniques of the nanopores. This review covers the important progress of nanopore fabrication in 2D materials and comprehensively compares these methods for the features of the introduced nanopores and their formation processes. Future perspectives are discussed on the opportunities and challenges in fabricating high-grade 2D nanopores.