<p>The central nervous system (CNS) has a unique relationship with the immune system, referred to as immune privilege. For many years it was thought that immune privilege was due to isolation of the CNS from the immune system, but recent findings have shown that this theory is flawed and that there is substantial neuroimmune communication, particularly at border sites that encase the CNS. These border sites include perivascular and subarachnoid spaces, the choroid plexus, the meninges and the vasculature, including the recently discovered meningeal lymphatic vessels. CNS border tissues have extensive interaction with the cerebrospinal fluid, which acts as an immune mediator, allowing the immune system at the CNS borders to respond to challenges within the CNS parenchyma. Together, CNS border tissues enable immune surveillance and protection against infections while preventing inflammatory damage to the parenchyma. A better understanding of the mechanisms of immune privilege as an accord, as opposed to isolation, between the two systems would help us obtain effective immunotherapies for neurological diseases.</p>