This article features the importance of nanomaterial-protein interfaces, with a special interest on two-dimensional (2D) nanomaterials, for next generation sensors and electronics. Graphene, the first isolated and studied 2D nanomaterial, is taken as the material of most interest and then focused on its engineering by heteroatom doping. The success of graphene engineering for sensors widened the search for better and efficient biosensor platforms of other layered materials such as boron nitride and transition metal dichalcogenides. But functionalization of 2D backbones with biomolecules often ends up with the disruption of the biological activities due to various reasons. This has to be fundamentally studied and corrected for the clinical implementation of these materials based novel sensing platforms in point-of-care devices and micro-fluidic chips. At the end, importance of various 2D materials-biomolecule interfaces is discussed, and MoS2 based label-free biosensor is highlighted. A method for the modification of MoS2-biomolecule interaction via covalent functionalization of oxygen functionalities in MoS2 is also proposed. Copyright © Materials Research Society 2015.