Atomically thin materials such as graphene and other 2D materials are promising for a wide range of applications. Mechanical interactions at the interfaces, including adhesion and friction, are critical for manufacturing (e.g., synthesis and transfer), integration, functional performance and reliability of these atomically thin materials. While van der Waals interactions have been commonly assumed to be the primary mechanism for the 2D materials, recent studies have suggested other mechanisms that may have to be considered, such as the effects of water capillary, reactive defects, and surface roughness. For adhesion and separation, in addition to the adhesion energy, the relation between the normal traction (attraction/repulsion) and the separation has been measured for some interfaces (e.g., graphene/Si), providing further insights into the underlying mechanisms associated with the strength and range of normal interactions. For friction or generally shear interactions, direct measurements are more challenging, but the critical shear strength has been reported for some interfaces (e.g., graphene/PET and graphene/Cu). Both normal and shear interactions are at play and coupled in the mixed-mode fracture experiments. This talk will first summarize the recent experimental efforts to characterize the mechanical interactions at the interfaces of 2D materials (mostly graphene). Theoretical models and MD simulations will be presented to provide qualitative understanding on the effects of surface roughness, water (wet adhesion) and temperature.