Abstract: Surface-enhanced Raman scattering (SERS) has been regarded as an attractive technique for efficient molecular sensing because of its nondestructive detection, fast response and high sensitivity. However, the majority of studies on SERS are still based on noble metals (e.g. Au, Ag), which suffer from the drawbacks of high-cost, low uniformity and poor stability, thus limiting their widespread use. Graphene shows an efficient SERS performance because of its two-dimensional (2D) atomically flat surface, large specific surface area, high stability and unique electronic/optical properties, which open up new avenues for SERS research. In recent years, other 2D inorganic layer materials, such as transition metal dichalcogenides (TMDCs), hexagonal boron nitride (h-BN), black phosphorus (BP), and MXenes, have also attracted increasing research attention. We summarize the SERS mechanisms and state-of-the-art progress on substrates based on 2D materials, including graphene and other 2D inorganic layer materials. The challenges and prospects for future research on high-performance SERS substrates are considered.