Background—In brain blood vessels, electrophysiological studies proving the existence of ATP-sensitive potassium channels (KATP) are scarce. However, numerous pharmacological studies establish the importance of KATPchannels in these blood vessels. This review emphasizes the data supporting the importance of vascular KATPin the responses of brain blood vessels.Summary of Review—Electrophysiological data show the existence of KATPin smooth muscle and endothelium of brain vessels. A much larger number of studies in virtually all experimental species have shown that classic openers of KATPdilate brain arteries and arterioles. This response can by blocked by glibenclamide, a selective inhibitor of KATPopening. Several physiological or pathophysiological responses are also blocked by glibenclamide. KATPcontains a multiplicity of potential sites of interaction with drugs of diverse, sometimes unrelated, structures. Drugs with imidazole or guanidinium groups are particularly likely to have effects on KATP. This complicates interpretation of the actions of such drugs when used as supposedly selective pharmacological probes for other putative targets. A pH-sensitive site on the internal surface of cloned channels may explain the glibenclamide-inhibitable dilation produced by intracellular acidosis and perhaps by CO2. In some situations KATPappears to be involved in either the synthesis/release or action of endothelium-derived mediators of cerebrovascular tone. The importance of KATPmay be dependent on the portion of the cerebrovascular tree being studied and on diverse experimental conditions, age, species, and the presence of disease.Conclusions—KATPhave been shown to mediate a wide range of cerebrovascular response in physiologic or pathologic circumstances in a variety of experimental conditions. Their relevance to cerebrovascular responses in humans remains to be explored.