Friction and wear are two physical processes that occur every time two surfaces contact each other and slide. The complexity of examining friction and wear arises because the chemistry of the interacting surfaces is complex and ill-defined and interactions between the surfaces are transient and not at equilibrium. Two dimensional (2D) materials, such as graphene, h-BN, and MoS2, reduce friction and wear of surfaces that change with the number of atomic layers present. Thus, it is possible control of the lubricating and wear properties of the sliding interface with great precision to describe these processes through physical models. However, several other factors, such as substrate adhesion, surface contamination, water intercalation, and the mechanical properties of the lubricant impact its friction and wear properties. Here, we will examine the impact of these additional factors on the ability for 2D materials to reduce friction and wear in sliding contacts.