Introduction: Subarachnoid hemorrhage (SAH) is associated with significant morbidity and mortality, even for patients who receive early neurointerventionist management. Areas covered: Early mechanisms of secondary brain injury precede the delayed vasospasm phase and contribute to the poor outcome. These mechanisms and their intervention are discussed, including high intracranial pressure (ICP), low cerebral perfusion pressure (CPP), acute vasospasm, disturbed cerebral autoregulation, cerebral edema, oxidative stress, seizures, microvascular damage and hyperglycemia. Erythropoietin, statins and magnesium have been particularly promising in experimental studies. Expert opinion: Multiple mechanisms, including delayed vasospasm, may contribute to cerebral ischemia and poor outcome following SAH. Treatments that simultaneously target multiple secondary injury pathways show significant potential as therapeutic agents, particularly those that attenuate vasospasm in addition to having other neuroprotective properties.