Considerable evidence links cerebral vasospasm to the decreased bioavailability of endothelial nitric oxide synthase (eNOS) after aneurysmal subarachnoid hemorrhage (SAH). In recent studies from the cardiology literature, researchers have suggested that a genetic predisposition to coronary vasospasm might develop as the result of a T-786C single nucleotide polymorphism (SNP) in the eNOS gene. The authors of this study attempted to determine if there may be a similar genetic predisposition toward cerebral vasospasm. The authors prospectively identified 28 patients with Fisher Grade 3 SAH from a group of 51 consecutive patients with ruptured intracranial saccular aneurysms. Genomic DNA was isolated from a peripheral blood sample obtained with permission from each patient. Gene microarray technology was used to assay the samples for the presence and distribution of certain key eNOS gene polymorphisms. Clinical, radiological, and genomic data were analyzed. The finding of eNOS T-786C SNP could be used to significantly differentiate between the presence and severity of cerebral vasospasm (p = 0.04). The findings from this preliminary study support similar findings in the coronary vasospasm literature as well as the hypothesis that a predisposition toward cerebral vasospasm may be related partially to genetic factors, which needs to be confirmed in a larger study. Such gene-based information may be important in rapidly identifying patients at increased risk of vasospasm after SAH, independent of their Fisher grade. In this article, the authors review key studies in this area.