Heat shock proteins (Hsps) are highly conserved ubiquitous proteins and are present both in prokaryotes and eukaryotes. They are essential for fundamental cellular processes and are induced in response to a wide variety of physiological and environmental stresses, allowing cells to survive in most adverse conditions. However, their basal expression in the absence of any stress demonstrates the important role they play in maintaining cellular homeostasis. So far, various functions of Hsps have been described including their role as a scaffolding protein, as molecular chaperones involved in folding and unfolding proteins, regulating cytoskeletal stability, cell cycle control, hormone signaling, important modulators of muscle contraction, cell migration, cell survival. They also play a role in antigen presentation and serve as death signals to help the immune system to recognize dead or damaged cells. Hsps regulate the activity of multiple intracellular signaling intermediates, many of which are involved in the execution of the apoptotic signaling pathways. Recently, interest has emerged to study the role of Hsps in the pathogenesis of various diseases including diabetes, renal fibrosis, neurodegenerative disorders, cardiovascular disease and cancer. This review describes in detail, the different functions of Hsps in health and disease. Taking into consideration, the wide variety of functions of Hsps in health and disease, Hsps have the therapeutic potential to serve in numerous clinical implications.