This chapter is a review of cerebrospinal fluid (CSF) studies that support the hypothesis that the disrupting effect of cerebral ischemia on certain central neurotransmitter systems may be responsible for the pathophysiological changes and deficits in brain function that complicate cerebrovascular disease. Any investigator interested in the precise mechanisms of disease should find the study of ischemic effects on brain function a daunting one. Even when the pattern of ischemia can, to a degree, be controlled, as it is in experimental models, the effects of reduced blood flow are catastrophic for the physiological function of many brain systems. Interpretation of the results is therefore hazardous at the outset and even more so in man, in whom ischemia is more often than not variable in onset, site, degree, and despite the advent of computed tomographic (CT) scanning, frequently difficult to define. Nevertheless, if, by examining the CSF, which is the “sink” for many products of brain metabolism, it can be determined that there is deviation from normality, then this primarily phenomenological approach can initiate and justify more extensive mechanistic studies in experimental animals, and with the development of positron-emission tomography, eventually in man.