Neurological diseases are often associated with cerebrovascular dysfunction and changes in blood-brain barrier (BBB) function. This is important for two seemingly conflicting reasons. On the one hand, a leaky BBB may lead to brain disease by allowing extravasation of cells and molecules normally segregated in the periphery, while on the other hand an intact BBB may hamper drug delivery to the ailing brain. Under both circumstances, it would be desirable to follow closely over time BBB "tightness". Several lines of evidence have suggested that the astrocytic protein S100beta is a potentially useful peripheral marker of BBB permeability. Other markers of brain-to-blood barriers have been recently discovered by a proteomic approach. These proteins are virtually absent in normal blood, appear in serum from patients with cerebral lesions, and can be easily detected. We will present clinical and laboratory evidence supporting the use of these markers as modern neurodiagnostic tools.