A brief analysis of the study of the running-in process is presented. The inconsistency of mechanistic representations of the running-in stage is established. An atomic and molecular model of tribological contact is presented. The mechanism of running-in is proposed, in which the main role is played by synthesis, in the process of which molecules, clusters, and nanosized particles are formed. By applying the Boltzmann transfer equation, an analytical expression for the evolutionary process of the exponential type of acclimation is obtained. The main characteristics of running-in are the running-in time and wear from the initial stage. The level of characteristics can be controlled by external factors (increasing the load in the process) and internal factors (structure of solids and lubricant).