The signal transduction of tumor necrosis factor-alpha (TNF-alpha) is complex and regulated via a vast number of interconnecting pathways. The TNF-alpha signaling pathway plays a major role in the pathogenesis of subarachnoid hemorrhage (SAH). The advent of molecular mimicry has provided a number of opportunities to tackle disease with improved specificity. Here we review the mechanisms of their action and the potential for TNF-alpha inhibitors as a treatment for subarachnoid hemorrhage. Searches were performed using PubMed with the search terms "subarachnoid haemorrhage", "TNF alpha", "novel drugs" TNF alpha inhibition", "management", "cerebral aneurysm", and "vasospasm' from 1970 to February, 2012. Articles were also identified through searches of the Cochrane library and searches of the authors’ own files. Only papers published in English were reviewed. In conclusion, there is considerable theoretical evidence for the potential of TNF-alpha inhibitors to impact on the pathogenesis of aneurismal SAH. Such indications demonstrate the potential for specific targeting of molecular signaling pathways to prevent the growth and rupture of cerebral aneurysm.