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Two-dimensional (2D) transition metal dichalcogenides (TMDs) hold immense promise as ultrathin-body semiconductors for cutting-edge electronics and optoelectronics. In particular, their sustained charge mobility even at atomic-level thickness as well as their absence of surface dangling bonds, versatile band structures, and silicon-compatibility integration make them a prime candidate for device applications in both academic and industrial domains. Despite such high expectations, group-VI TMDs reportedly exhibit a range of enigmatic properties, such as substantial contact resistance, Fermi level pinning, and limited unipolar charge transport, which are all rooted in their inherent defects. In other words, intrinsic physical properties resulting from their native defects extend their influence beyond the material level. Bridging point-defect-induced material properties and their behavior at the device level, this Perspective sheds light on the significance of crystalline defects beyond a rather simple defect–property relationship. As a distinctive approach, we briefly review the well-established defect model of conventional III–V semiconductors and further apply it to the emergent defect behaviors of 2D TMDs such as their defect-induced gap states. Within the main discussion, we survey a range of behaviors caused by the most prevalent intrinsic defect, namely, vacancies, within 2D TMDs, and their implications for electronic and optoelectronic properties when employed at the device level. This review presents an in-depth summary of complexities in material properties as well as device characteristics arising from intrinsic point defects and provides a solid foundation for the cross-links among native defects and material/device properties. [ABSTRACT FROM AUTHOR]