Skeletal muscle is one of the most important tissues of the human body. It comprises up to 40% of the body mass and is crucial to survival. Hence, the maintenance of skeletal muscle mass and strength is pivotal. It is well-established that resistance exercise provides a potent anabolic stimulus to increase muscle mass and strength in men and women of all ages. Resistance exercise consists of mechano-biological descriptors, such as load, muscle action, number of repetitions, repetition duration, number of sets, rest interval between sets, frequency, volitional muscular failure, and range of motion, which can be manipulated. Herein, we discuss the evidence-based contribution of these mechano-biological descriptors to muscle mass and strength.