ConspectusTwo-dimensional (2D) transition-metal dichalcogenides (TMDs) are a class of promising low-dimensional materials with a variety of emergent properties which are attractive for next-generation electronic and optical devices; such properties include tunable band gaps, high electron mobilities, high exciton binding energies, excellent thermal stability and flexibility. During the synthesis process of these materials, especially chemical vapor deposition, defects such as grain boundaries (GBs) inevitably exist. GBs are the interfaces between differently oriented grains and are line defects in 2D crystals. While GBs can degrade the overall quality of 2D materials and adversely affect some of their electrical and mechanical properties, recent results show that GBs give rise to or enhance a wide range of unique electrical, mechanical, and chemical properties of the GBs in 2D TMDs. The effects of GBs on 2D material properties are complex and diverse, providing exciting opportunities to realize new functionalities by manipulating the local structure and properties. Notably, these effects are strongly related to atom types, dislocation cores, crystal misorientation at GBs, and both in- and out-of-plane deformation. The exploitation of GBs for novel applications requires a deepened understanding of synthesis, postprocessing, defect structures, GB properties, and GB structure-property relationships in 2D materials.In this Account, we first introduce a detailed classification of GBs in 2D TMDs based on atomic structure, symmetry, and the local coordination of both transition metals and chalcogenide atoms. The GB types in typical MoS2 (high-symmetry hexagonal structure) and ReS2 (low-symmetry monoclinic structure) are taken as examples. Next, we describe the properties of GBs in 2D TMDs, including thermodynamic and kinetic, mechanical, thermal, electrical, magnetic, chemical, and electrocatalysis properties as well as several application areas where these may be exploited. Here we provide systematic atomic-level and electronic level explanations of these properties to clarify their dependences on GB structures. Applications that extend from these properties, including functional electronics, chemical sensors, and electrocatalysts, are also described. Finally, we provide several perspectives and suggest promising opportunities for exploiting the novel properties of GBs in 2D TMDs. We expect that this Account will further stimulate the fundamental research of GBs and boost the wide application of multifunctional devices.