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Molecular chaperones are ubiquitous and abundant within cellular en-vironments, functioning as a defense mechanism against outer environ-ment. The range of molecular chaperones varies from 10 to over 100 kDa. Depending on the size, the specific locations and physiological roles of molecular chaperones vary within the cell. Multifunctionality of heat shock proteins (HSPs) expressed via various cyto-stress including heat shock have been spotlighted as a reliable prognostic target bio-marker for therapeutic purpose in neuromuscular disease or cancer re-lated studies. HSP also plays a critical role in the maintenance of pro-teins and cellular homeostasis in exercise-induced adaptation. Such various functions of HSPs give scientists insights into intracellular pro-tective mechanisms in the living body thus HSPs can be target mole-cules to know the defense mechanism in cellular environment. Based on experimental results regarding small to large scaled HSPs, this re-view aims to provide updated important information regarding the mo-dality of responses of intracellular HSPs towards extracellular stimula-tions. Further, the expressive mechanisms of HSPs data from tremen-dous in vivo and in vitro studies underlying the enhancement of the functionality of living body will be discussed.