Aneurysmal subarachnoid hemorrhage (SAH) is analogous to a pathophysiological watershed, disrupting brain integrity and function and precipitating an array of systemic derangements including cardiovascular, respiratory, endocrine, hematological, and immune dysfunction. Extracerebral organ dysfunction is closely linked to the magnitude of the primary neurological insult, suggesting neurogenic, neuroendocrine and neuroimmunomodulatory mechanisms. Systemic organ involvement is associated with increased mortality and neurological impairment, even after adjustment for other outcome predictors such as the severity of the initial neurological injury. This may be a reflection of secondary brain injury precipitated by hypoxemia, circulatory failure, fever, or hyperglycemia, all of which have been linked to adverse clinical outcomes. Interventions to avert or reverse these and other perturbations need to be tested in clinical trials as they represent opportunities to improve survival and neurological recovery in patients with SAH.