Type 2 diabetes is a metabolic disorder characterized by high levels of bloodglucose, insulin resistance and hyperinsulinemia. These metabolic alterations may causevascular changes resulting in a reduction of oxygen delivery to cells, a phenomenoncalled hypoxia. Hypoxia could be a double-sided coin, since it is able to activatepathways controlling cell survival or death. It was showed that short periods of hypoxiamay be protective however chronic hypoxia activates pro-death pathways. The brain is ahighly metabolic active organ requiring a continuous supply of glucose and oxygen.Because the brain consumes 20% of total oxygen consumed by the body, it is verysusceptible to changes in oxygen levels. It has been postulated that chronic hypoxia isintimately associated with type 2 diabetes and potentiates neurodegenerative diseases,namely Alzheimer's disease. This chapter aims to discuss the molecular mechanismsunderlying hypoxia and its involvement in the pathologic processes of diabetes andAlzheimer's disease.