Investigating novel 2D material systems by means of modeling and simulation is of paramount importance, as the current understanding of 2D-material devices has been largely limited partly due to many barriers in direct experiments. Here we will discuss the state of the art in numerical simulations for 2D-material device applications. Several approximations to describe the electronic properties of layered materials shall be introduced and the trade-off will be analyzed. Using self-consistent quantum transport simulations based on non-equilibrium Green’s function (NEGF) method, we investigate 2D semiconductors such as MoS2, BP and GeH for different target applications: low-power and high-performance electronics as well as high-frequency applications. In addition, we will also discuss the design strategy for 2D material electronics, considering the number of layers.