Ischemia is a blockage of blood supply due to an embolism ora hemorrhage in a blood vessel. When an organ cannot receiveoxygenated blood and can therefore no longer replenish itsblood supply due to ischemia, stresses, such as the disruptionof blood glucose homeostasis, hypoglycemia and hypoxia,activate the AMPK complex. LKB1 and CaMKKβ are essentialactivators of the AMPK signaling pathway. AMPK triggersproangiogenic effects through the eNOS protein in tissues withischemic conditions, where cells are vulnerable to apoptosis,autophagy and necrosis. The AMPK complex acts to restoreblood glucose levels and ATP levels back to homeostasis. Thisreview will discuss AMPK, as well as its key activators (LKB1and CaMKKβ), as a central energy regulator and evaluate theupstream and downstream regulating pathways of AMPK. Wewill also discuss how we can control this important enzyme inischemic conditions to prevent harmful effects in patients withvascular damage.