Actuators are essential components for motion in machines, and warranty service lives are basic specifications of actuators. However, fatigue damage or wear of actuators are very complex and related to many design factors, such as materials properties, surface conditions, loads, and operating temperature. Actuator manufacturers still rely heavily on physical experiments to determine the fatigue lives of actuators. This paper investigates the state-of-the-art of using numerical simulations for fatigue analysis of mechanical actuators. Failure criteria of machine elements are discussed extensively; existing works on using finite element methods for machine element designs are examined to (1) explore the feasibility of using a numerical simulation for fatigue analysis and (2) discuss the technical challenges in practice. Moreover, a systematic procedure is suggested to predict fatigue lives of mechanical actuators with Teflon impregnated hard coatings. A virtual fatigue analysis allows for optimizing a mechanical structure, reducing design verification costs, and shortening the development time of actuators.