Blood-brain barier (BBB) segregates central nervous system (CNS) from the circulating blood. BBB is formed by the brain capillary endothelial cells with complex tight junctions between them as well as by astrocytes and pericytes. BBB is responsible for transport of selected chemicals into and out of the CNS as well as for its protection from fluctuations in plasma composition following meals, during exercise and from circulating agents such as neurotransmitters, xenobiotics and other potentially harmful substances capable to disturb neural function. BBB may be compromised during CNS injury, infection, fever and in some nerodegenerative diseases. The increase of BBB permeability was observed also during exercise as documented by changes of plasma S-100 protein levels, used as a peripheral marker of BBB integrity. Marked change in BBB integrity during exercise may disturb normal brain function and contribute to the development of central fatigue. Moreover, serum S-100β may indicate level of injury in individuals suffering brain injuries during sports. There are also data suggesting that acute effect of physical exercise on serum S100β levels may not be related with CNS injury. Further studies to establish whether training and which type of it may modulate BBB permeability are needed.