Hypertension remains a leading cause of cardiovascular morbidity, mortality, and disability worldwide. It is also a significant modifiable factor contributing to chronic brain damage. Key mechanisms involved in this process include cerebral microangiopathy, endothelial dysfunction, impaired autoregulation of cerebral blood flow, and oxidative stress. These factors play a central role in the development of chronic cerebral ischemia and cognitive impairment. This article reviews published data on the impact of oxidative stress and metabolic disturbances on hypertensive brain injury, as well as current approaches to neuroprotective therapy. Particular attention is given to ethylmethylhydroxypyridine succinate (Mexidol), an agent with a multimodal mechanism of action. Experimental and clinical studies are reviewed, including the results of the randomized placebo-controlled MEMO trial and its subgroup analysis involving patients with hypertension. The evidence presented supports the sequential therapy with Mexidol in this patient population, aimed at preventing the progression of cognitive impairment.