Background. Brain-derived neuro-trophic factor (BDNF), a major neurotrophin, and vascular endothelial growth factor (VEGF) have a documented role in neurogenesis, angiogenesis, and neuronal survival. BDNF can benefit infarct size and functional motor recovery after an ischemic brain lesion in stroke. BDNF also appears to be involved in the pathogenesis of several cardiometabolic disorders, indicating that it is important in brain-body dysfunctions. This review examines the available evidence about the role of BDNF in the development of cardiometabolic vascular risk. Methods. Internet search and discussion with peer colleagues. Results. Several studies have demonstrated that phenotypes associated with insulin resistance are at increased risk for developing cognitive decline and neurodegeneration, vascular dementia, depression and diabetes mellitus and metabolic syndrome which are risk factors for CVDs. BDNF is a member of the neurotrophin family, which interacts with high affinity with tyrosine receptor kinase B and is abundantly expressed in central and peripheral nervous system and can cross the blood-brain barrier in both directions. Majority of the BDNF (70-80%) is derived from brain but it is also present in other body tissue. Apart from lipid and glucose metabolism, BDNF also controls the food intake and appetite. Lower serum BDNF and higher VEGF concentrations were associated with increased risk of incident stroke/TIA. BDNF and VEGF seem to be novel risk markers and may improve stratification of patients at risk for stroke/TIA. Increased concentrations of BDNF were also associated with less white matter hyperintensity and better visual memory. BDNF may serve as an intermediate biomarker for subclinical vascular disease. It may have biological potential to serve as a therapeutic target for primary and secondary prevention of cardiometabolic risk as well as clinical and subclinical vascular brain disease. BDNF deficiency has been observed in association with depression and type 2 diabetes and vascular diseases. BDNF administration may be protective and may have a beneficial influence on BDNF concentrations, insulin receptors and hypothalamic dysfunction leading to beneficial effects on cardiometabolic risk. Moderate physical activity may increase BDNF release. Conclusion. The findings suggest that circulating BDNF deficiency is a risk factor for cardiometabolic risk and vascular diseases. BDNF administration may modify the risk of clinical and subclinical vascular brain injury, type 2 diabetes and vascular disease. © 2016 Nova Science Publishers, Inc.