The brain and spinal cord are surrounded by cerebrospinal fluid, which provides a mechanically stable environment for these delicate structures against the forces of gravity and sudden acceleration and deceleration. Neurons and glia comprising the parenchyma of the brain are enveloped in their microenvironment by interstitial fluid. Interstitial fluid has long been considered to be unaffected by the production and flow of cerebrospinal fluid outside the brain parenchyma. However, two recent papers by Iliff et al. demonstrate that cerebrospinal fluid enters the deep substance of the brain, mixes with the interstitial fluid surrounding neurons and glia, and plays an important role in the exchange and clearance of molecules in the interstitial space of the central nervous system.