Surface-enhanced Raman scattering (SERS) has been adopted as a useful analytical technique to quantitatively determine the bio-/chemical analytes with fingerprint recognition and non-destructivity in various fields. However, the well-developed SERS substrates are mostly noble metals, which are expensive, difficult for mass production, irreproducible and unstable in long run. To overcome these disadvantages, various two-dimensional (2D) materials have recently been developed to serve as substrates for SERS due to their low cost, easy synthesis, outstanding optical properties and good biocompatibility. Moreover, 2D materials show unique and excellent physicochemical properties, such as tunable electronic structures, high carrier mobility, chemical inertness, and flexibility. Herein, we review recent advances of 2D-material-based SERS substrates, with a special focus on the effects of composition and structure on the sensitivity and stability. The principles and applications of 2D materials in SERS enhancement are summarized and systematically discussed. Finally, the challenges and perspectives of these 2D materials are proposed, orienting improved SERS performance and expanded applications. This work may arouse more awareness on design of 2D-material-based SERS substrates for in-depth study and practical applications.