Pain perception and pain modulation varies between individuals. For example, pain perception and pain modulation vary extensively between endurance athletes and non-athletes. Compared to non-athletes, endurance athletes perceive noxious stimuli as less painful, and they possess a greater effect of conditioned pain modulation (CPM) which is associated with their weekly training capacity. These two findings indicate a more efficient system of endogenous pain inhibition in endurance athletes. The present Ph.D. project aimed to systematically investigate the processing and, for the first time, the neural mechanisms of pain in endurance athletes. To achieve this aim, the behavioral as well as the neural level of pain processing was compared between endurance athletes and non-athletes in three studies. The first study examined the effectiveness of the endogenous pain inhibition system in endurance athletes and non-athletes by conducting a CPM paradigm and a placebo paradigm. The second study investigated differences in the activation and the functional connectivity of brain regions that are typically activated by nociceptive stimulation during painful heat stimulation using functional magnetic resonance imaging. The third study explored the microstructure of brain white matter using diffusion magnetic resonance imaging. The white matter tract of interest was the medial forebrain bundle (MFB), a major white matter tract of the pain system that connects the basal forebrain with the brain stem. The results of each of the three studies confirmed that endurance athletes perceive noxious stimuli as less painful. In summary, the results of the present Ph.D. project provide valuable insights in the neural mechanisms of altered pain processing in endurance athletes and therewith offer a wealth of starting points for future studies and hypotheses. A highly promising hypothesis to follow up is to test whether or not endurance sport could prevent chronic pain.