Two-dimensional (2D) nanosheets with atomic thickness have attracted a great deal of research interests, due to their extraordinary optical, electronic and mechanical properties for promising applications, such as sensor, electronics, biomedicine, catalysis and energy storage. However, because of the difficulties in the preparation of atomically thick 2D nanosheets, especially for the materials with non-layered structures, current research interests mainly focused on the limited layered samples. Furthermore, owing to the lack of executable characterization techniques for obtaining accurate structural information of ultra thin 2D nanosheets, it is still challenging to understand the correlations between the atomic/electronic structures and their intrinsic properties. In this review, we focus on the recent progresses in synthetic strategies of ultrathin 2D nanosheets, especially for the materials with non-layered structures, and survey effective methods for the regulation of the electronic structures of these ultrathin 2D nanosheets. In addition, we also highlight the clear structure-property relationships of ultrathin 2D nanosheets and overview their applications in photocatalysis, electrocatalysis, energy storage device, electronic device and biological area. Finally, on the basis of the current progresses, the major challenges and opportunities on ultrathin 2D nanosheets are also presented, which could bring new opportunities for future research in the field of chemistry. (C) 2016 Elsevier Ltd. All rights reserved.