The BH3 interacting domain death agonist (BID), containing only the BH3 domain, is a pro-apoptotic member of the Bcl-2 protein family. BID is important to cell death mediated by Bcl-2 family proteases and thus is the sentinel to protease-mediated death signals. In response to apoptotic signaling, BID interacts with another Bcl-2 family protein, Bax, leading to the insertion of Bax into organelle membranes, primarily the outer mitochondrial membrane. The expression of BID is upregulated by the tumor suppressor p53, and BID has been shown to be involved in p53-mediated apoptosis. Recent studies further indicate that BID may be more than just a killer molecule, it could be also involved in the maintenance of genomic stability by engaging at mitosis checkpoint. BID is a key regulator of the intrinsic death pathway that amplifies caspase-dependent and caspase-independent execution of neuronal apoptosis. Therefore pharmacological inhibition of BID provides a promising therapeutic strategy in neurological diseases where programmed cell death is prominent.