Introduction We recently showed the thermotolerance of animal somatic cells to a lethal temperature and this tolerance was associated with morphological and molecular changes. Notably, heat shock proteins (Hsp) play an important role in the process of thermotolerance. In this chapter, we briefly highlight the essential roles of Hsp in resisting lethal temperatures and regaining the cellular vitality during the recovery from heat shock. Methods A literature-based collection of articles in the available search engines (PubMed and Google Scholar). Results We show the critical roles of Hsp in antagonizing the pathways of apoptosis and the involvement of several other proteins in the cellular resilience or anastasis. Conclusions Modulating the pathways of anastasis through Hsp would permit therapeutic targets for either promoting (such as female folliculogenesis) or hindering anastasis for tumor therapy.