Loss of cerebrospinal fluid (CSF) occurs commonly in daily neurosurgical practice. Understanding the altered physiology following CSF loss is important for optimization of patient care and avoidance of complications. There is overwhelming evidence now that the cerebral venous system plays a major role in intracranial pressure (ICP) dynamics especially when one takes into account the effects of postural changes, atmospheric pressure, and gravity on the craniospinal axis as a whole. The CSF and cerebral venous compartments are tightly coupled in two important ways. CSF is resorbed into the venous system, and there is also an evolved mechanism that prevents overdrainage of venous blood with upright positioning known as the Starling resistor. With loss of CSF pressure, this protective mechanism could become nonfunctional which may result in posture-related venous overdrainage through the cranial venous outflow tracts leading to pathologic states. This review article summarizes the relevant anatomic and physiologic basis of the relationship between the craniospinal venous and CSF compartments in the setting of CSF diversion. It is hoped that this article improves our understanding of ICP dynamics after CSF loss, adds a new dimension to our therapeutic methods, stimulates further research into this field, and ultimately improves our care of these patients.