The mechanisms underpinning fatigue and exhaustion, and the specific sources of exercise-endurance intensity regulation and (in)tolerance have been investigated for over a century. Although several scientific theories are currently available, over the past five years a new framework called Psychobiological model has been proposed. This model gives greater attention to perceptual and motivational factors than its antecedents, and their respective influence on the conscious process of decision-making and behavioral regulation. In this review we present experimental evidences and summarize the key points of the Psychobiological model to explain intensity regulation and (in)tolerance in endurance exercise. Still, we discuss how the Psychobiological model explains training-induced adaptations related to improvements in performance, experimental manipulations, its predictions, and propose future directions for this investigative area. The Psychobiological model may give a new perspective to the results already published in the literature, helping scientists to better guide their research problems, as well as to analyze and interpret new findings more accurately.