Historically, determination of the critical cerebral perfusion pressure (CPP) was done in animals by a progressive lowering of arterial pressure yielding a nominal critical CPP of 60 mmHg. Subsequently, it was shown that if the CPP was decreased by increasing intracranial pressure (ICP), critical CPP fell to 30 mmHg. This discrepancy was unexplained. We recently provided evidence that the decrease in critical CPP was due to microvascular shunting resulting in maintained cerebral blood flow (CBF) at a lower CPP. We demonstrated by a progressive increase in ICP in rats using two-photon laser scanning microscopy (2PLSM) that the transition from capillary to microvascular shunt flow is a pathological process. We surmise that the loss of CBF autoregulation revealed by decreasing arterial pressure occurs by dilation of normal cerebral blood vessels whereas that which occurs by increasing ICP is due to microvascular shunting. Our observations indicate that the loss of CBF autoregulation we observed in brain injured patients that changes on an hourly or daily basis reflects an important pathophysiological process impacting on outcome that remains to be determined.