This chapter focuses on the cerebrospinal fluid (CSF) compartment within the central nervous system (CNS). It builds upon the discussions of body fluid compartments in the preceding chapters. CSF is traditionally described as a clear, colorless liquid that surrounds the brain and spinal cord parenchyma, providing mechanical and chemical protection to these delicate structures, among other functions. Three major aspects of CSF stand out in the scientific literature: CSF generation, CSF motion (or circulation), and CSF absorption. All three areas of CSF physiology present knowledge gaps, which contribute to ongoing controversy. One of the few certainties regarding CSF is that most neurological disorders are linked to CSF pathophysiology. CSF delivers nutrients to the CNS and plays a crucial role in clearing toxic metabolites from the brain and spinal cord into the venous system, either directly or indirectly via the lymphatic system. Abnormalities in CSF physiology can lead to the accumulation of toxic substances in neural tissues, such as amyloid- \(\beta \) (A \(\beta \) ) and tau, which are central to the pathogenesis of Alzheimer’s disease. In this chapter, we first identify the CSF spaces in the CNS and describe the formation and composition of CSF. We then explore CSF dynamics and its functions in CNS physiology. Following that, we discuss two major recent discoveries relevant to CSF physiology: the meningeal lymphatic system and the glymphatic system. The next two sections specifically address CSF in the spinal canal and associated pathologies. The final section integrates all major CNS extracellular fluid compartments and their interactive dynamics, using an MRI study of a patient with idiopathic intracranial hypertension (IIH) and a healthy control for comparison. The chapter concludes with a summary and suggestions for further reading.