This article discusses the biophysical aspects of venous outflow from the brain in healthy individuals and in patients with chronic cerebrospinal venous insufficiency. Blood flows out of the brain differently, depending on body position. In the supine position it flows out mainly through internal jugular veins, while in the upright position it uses the vertebral veins. This phenomenon is probably not due to the active regulation of the flow but instead results from the collapse of jugular veins when the head is elevated. Such a collapse is associated with a significant increase in flow resistance, which leads to redirection of the flow towards the vertebral pathway. Theoretical calculations respecting the rules of fluid mechanics indicate that the pressure gradients necessary for moving blood from the brain toward the heart differ significantly between the supine and upright positions. The occlusion of internal jugular veins, according to fluid mechanics, should result in significant increase in the flow resistance and the restriction of cerebral flow, which is in line with clinical observations. Importantly, the biophysical analysis of cerebral venous outflow implies that the brain cannot easily compensate for increased peripheral venous resistance (namely, an occlusion of the large extracranial veins draining this organ), either by elevating the pressure gradient or by decreasing the vascular resistance through the recruitment of additional drainage pathways. This may mean that chronic cerebrospinal venous insufficiency may cause the destruction of the delicate nervous tissue of the central nervous system.