A number of intrinsic factors are present intracellularly and could be turned on to protect cells from stress and injury, including cerebral ischemia. The degree of protection of these factors is dependent on the time of induction, their concentration, as well as the duration and extent of injury. This review summarizes recent studies on some of the protective factors with specific emphasis on two recently discovered intrinsic protective proteins: 14-3-3gamma protein and neuroglobin. Both of them were originally discovered in neurons, later identified in astrocytes under ischemic conditions, and demonstrated to have protective effect on nerve cells from apoptosis. Understanding the mode of induction and role of protection of these intrinsic protective proteins would be beneficial for the future development of pharmacotherapy in extending the therapeutic time window, which would lead to better stroke management for patients.