Tribology covers all the phenomena occurring at the interfaces between objects, such as friction, wear, and adhesion. Human senses can only perceive tribological behavior on the macroscale, but the phenomena are actually determined by the dynamics of numerous surface asperities on the microscale and nanoscale. The multi-asperity dynamics, namely the sum of the responses of each single asperity on the sliding surfaces, are very complicated; thus, the macroscale behavior cannot be predicted precisely at this time. Hence, tribologists generally design surfaces via atrial-and-errorstrategy. Even though thetrial-and-errorstrategy is generally accepted, understanding the tribological phenomena caused by a single-asperity contact on the microscale and nanoscale is still important, because certain mechanisms usually dominate the macroscale phenomena. By identifying the dominant mechanisms, we can satisfactorily control the macroscale friction and wear. Recently, two-dimensional (2D) materials have attracted considerable interest in the field of tribology owing to their extraordinary properties, such as their thinness, lubricity, chemical stability, thermal conductivity, elastic modulus, and fracture strength. The trend toward securing functionally designed surfaces and the ever-increasing improvement of the lubrication performance of industrial machinery have led to significant progress in identifying the tribological mechanisms on the microscale and nanoscale and utilizing 2D materials as lubricants on the macroscale. In this work, we review reports on the basic mechanisms of and recent results of research on nanoscale friction in 2D materials and summarize the achievements and challenges in the macroscale application of 2D materials as lubricants. Finally, we highlight superlubricity as the property that ensures the longevity of 2D material-based solid lubricants.