The neurovascular unit which comprises the microenvironment within small blood vessels in the brain parenchyma is responsible for the maintenance of normal neuronal function by a continuous supply of nutrients. Inflammatory processes and loss of brain–blood-barrier (BBB) integrity can lead to vascular dysfunction and pathological interactions between microvasculature, neurons, and astrocytes. These events have been closely related to the development of brain disorders such as cognitive decline, supported by numerous studies using hypertension animal models. There is a large body of evidence showing the implication of circulating and local renin angiotensin system in cerebral microvasculature function. Angiotensin II, trough AT₁ receptor activation, has been related to elevated reactive oxygen species production, endothelial dysfunction, elevated permeability, inflammatory events, and vascular structure alterations. The angiotensin receptor blockers, used in antihypertensive treatments, are an important pharmacologic tool with neuroprotective effects because they can modify vascular damage and improve cognitive alterations. The development of vascular diseases can be influenced and promoted by external factors such as stress and drug abuse. Stress is related to induction of structural changes in arteries and cytokine production leading to endothelial damage and inflammation. It is known that psychostimulants have cardiovascular stimulant effects that can promote cerebral vasculitis and intracranial hemorrhage by direct and indirect mechanisms on the vasculature. The brain renin–angiotensin system is becoming an interesting new therapeutic target for vascular and related cognitive disorders.