Two-dimensional (2D) selenium was synthesized successfully in 2017. Its advanced properties, including size-dependent bandgap, excellent environmental robustness, strong photoluminescence effect, anisotropic thermal conductivity, and high photoconductivity, render it and selenium-based composites a promising candidate for various device applications. These include batteries, modulators, photodetectors, and photothermal effects in medical applications. However, compared to other commonly used 2D materials, such as graphene, transition metal dichalcogenides, and black phosphorus, 2D Se is much less known. Motivated by the need to overcome this lack of knowledge, this article focuses on recent progress and elucidates the crystal structure, synthesis methods, physical properties, applications, challenges, and prospects of 2D Se nanoflakes.