Skeletal muscles are the main motional force of the human body. Their distribution throughout the body allows different types of movements and contractions needed to interact with the environment. Therefore, understanding skeletal muscle function, their contractions, and force production are very important to optimize their efficiency. This paper aims to describe the activation and work of skeletal muscles, and the causes and signs of fatigue and overtraining, as well as possible treatments in their prevention and healing. Fatigue is a condition in which a muscle can not maintain maximum contraction, and its effectiveness decreases. There are various causes of fatigue, and they can be a consequence of the changes in the motor neuron, signal transmission to the muscle, or from the muscle cell, which is described in this paper. The main cure for fatigue is rest. A condition of prolonged fatigue accompanied by numerous signs of impaired health is called an overtraining syndrome. This paper describes the causes, manifestations, and possibilities of prevention and treatment of this condition. The main conclusion of this paper is the great importance of the rest for health and maximum skeletal muscle efficiency.