There is a rapidly growing literature using fMRI technology to investigate the various forms of behavioral impairment associated with brain injury and disease. Given this, surprisingly little work has been conducted to examine the influence of neuropathophysiological processes on the fMRI signal. This paper reviews the literature examining baseline alteration in cerebrovascular parameters associated with normal aging, brain injury, and brain disease. In addition, findings from three cases of individuals with severe brain trauma will be presented to show the influence of brain trauma on baseline cerebrovascular parameters measured by fMRI. The methods used here can be implemented by other investigators to accurately isolate specific hemodynamic changes that can influence the BOLD fMRI signal.