Resistance exercise is a popular form of conditioning for numerous sport disciplines, and recently different modes of strength training are being evaluated for health benefits. Resistance exercise differs significantly in nature, and several variables determine the direction and range of adaptive changes that occur in the muscular and skeletal system of the body. Some modes of resistance training can also be effective in stimulating the cardiovascular system. These variables include exercise selection (general, specific, single or multi joint, dynamic, explosive), type of resistance (free weights, variable resistance, isokinetics), order of exercise (upper and lower body or push and pull exercises), and most of all the training load which includes intensity expressed as % of 1RM, number of repetitions, number of sets and the rest interval between sets. Manipulating these variables allows for specific adaptive changes which may include gains in muscle mass, muscle strength or muscle endurance. It has been well established that during resistance exercise fatigue occurs, regardless of the volume and intensity of work applied. The peripheral mechanisms of fatigue have been studied and explained in more detail than those related to the CNS. This review is an attempt to bring together the latest knowledge regarding fatigue, both peripheral and central, during resistance exercise. The authors of this review concentrated on physiological and biochemical mechanisms underlying fatigue in exercises performed with maximal intensity, as well as those performed to exhaustion with numerous repetitions and submaximal load.