Covalent organic frameworks (COFs) are crystalline and porous materials with bi- or three-dimensional structures built up by connecting their molecular precursors by dynamic covalent bonds. Using bottom-up or top-down strategies, bi-dimensional COFs can be obtained as single- or few-layer materials, thus enlarging the family of 2D-materials based on graphene. The main advantage of 2D-materials based on COFs is the fact that they can be chemically designed, thus allowing the formation of á la carte materials with well-designed functionalities including their size and features of their pores. The aim of this perspective review is to illustrate in a rational way the current state-of-the-art in the field of COF nanosheet formation using the two general approaches of material nano-structuring. This article reviews a selected collection of samples that illustrates the essential concepts, strategies of preparation following the two general approaches, bottom-up and top-down, and a selection of COF nanolayers showing seminal properties and potential material applications. Finally, we provide some perspectives of this novel research field.