Inflammation is essential for immunity against invading pathogens and for initiating tissue repair after injury. The normal balance between pro and anti-inflammatory mechanisms usually leads to a timely resolution of this response.  Our bodies develop a systemic inflammatory response following significant surgical trauma through the release of proinflammatory mediators and triggering of neuroendocrine mechanisms.  There may be temporary disruption of the blood brain barrier leading to exposure of the brain to proinflammatory mediators, and in combination with activation of neuroinflammatory pathways, may result in neuroinflammation.  While neuroinflammation can confer benefits after a cerebral injury or insult, it can inflict unintended harm when it is misdirected, prolonged or maladaptive.   There is ample evidence of neuroinflammation in neurodegenerative conditions such as Alzheimer’s disease.  Neuroinflammation lacks obvious advantages in the postoperative period when the brain is not the site of surgery, but it may contribute to the development of delirium, more subtle forms of cognitive dysfunction or may accelerate the decline of those suffering from pre-existing neurodegenerative conditions.  There is a large body of preclinical research aimed at unravelling the responsible mechanisms responsible for initiating or perpetuating postoperative neuroinflammation, in order to provide more specific therapeutic approaches to be evaluated clinically.  On the other hand, translational research is thwarted with many challenges.  In this lecture, I will provide an overview of our current understanding of the mechanisms underlying postoperative neuroinflammation and its neurological consequences.  I will also review the effects of existing medications and potential therapeutic approaches that are being explored for their effects on postoperative neuroinflammation.