Nontraditional risk factors for cerebrovascular disease are rapidly emerging. The categories are expanding, and include those related to infection, inflammation, sleep disorders, hemostasis, nutrition, endocrine, and ones individual genotype. Many of the promising factors lack large randomized prospective population studies confirming direct cause and effect. However there have been strong evidence supporting increased stroke risk factor for infection, obstructive sleep disorders, the metabolic syndrome and impaired glucose tolerance in particular. Unique drug targets have already been identified in some of these emerging risk factors. The complexity of the pathophysiology of this disease remains a challenge. For example despite repeated evidence of estrogen-related neuroprotection, large populationbased studies in postmenopausal women receiving estrogen replacement did not demonstrate the expected neuroprotection. This suggests that aggressive research both at the basic science and transitional level needs to evolve, to ensure targeted successful stroke therapy. The advent of nanotechnology including the development of targeted therapeutic nanospheres, and of revolutionary molecular technology resulting in the synthesis of specific peptide mimetics, bodes well for the future development of cerebrovascular drug treatment.