The blood-brain barrier (BBB) is selectively permeable and shows a wide range of permeability to various substances in health and becomes generally permeable to all small molecules in almost all disease states. The capillary bed in brain (the BBB) is uniquely impermeable to many polar substances. The mechanism by which the capillary bed is maintained in this state is unknown, but may be an astrocytic function. In most major neuropathology, the BBB is lost because these unique structural features creating the BBB come to resemble the permeable capillaries in other tissues. Early isotopic brain scans using polar isotopes such as 99m-TcO4 depend upon this increased permeability to demonstrate focal lesions. Positron emission tomography has made it possible to label interesting biochemical substrates allowing the tracing of certain aspects of regional brain metabolic activity. The equipment required is very expensive, but single photon tomography using lipophilic tracers is much less expensive and provides tomographic representation of regional blood flow. To penetrate a healthy BBB requires that radiotracers either be lipid soluble or have an affinity for one of the selective BBB transport systems.