The blood-brain barrier (BBB) is formed by high resistance tight junctions within the capillary endothelium perfusing the vertebrate brain. Normal BBB maintains a unique microenvironment within the central nervous system (CNS). In neurodegenerative disorders (for example multiple sclerosis, MS), the BBB becomes impaired. Perivascular cells (astrocytes, macrophages and microglial cells) and brain microvascular endothelial cells (BMEC) produce various inflammatory factors that affect the BBB permeability and the expression of adhesion molecules. Indeed, cytokines can stimulate the expression of several adhesion molecules on brain microvascular endothelial cells. Among these adhesion molecules, the intercellular adhesion molecule-1 (ICAM-1) binds to its leukocyte ligands and allows activated leukocytes entry into the CNS. This review is dealing with the expression and regulation of ICAM-1 in relation with several properties of the BBB. Particularly, the role of ICAM-1 in the control of the leukocyte traffic into the CNS, as well as in cerebral malaria and in CNS infection by viruses, is discussed.