Heat-shock proteins (HSP) represents a protein superfamily comprising distinct molecular weights which are synthesized under conditions of cellular stress. The HSP constitute a phylogenetically-conserved response of cell preservation. Their functions are related to mechanisms such as thermotolerance and transport and scavenging of intracellular peptides. Some recent experimental evidence suggests that HSP participate directly in immune responses perhaps facilitating the recognition of exogenous antigens, and its levels are raised in inflammatory situations. Their pathogenic role in the chronic inflammation is still unclear, but the HSP could intervene as immunodominant antigens, mimicking structural proteins or evading the so-called immunological memory. In this review, we update the information concerning the relevance of HSP in medicine and discuss its potential role in autoimmune mechanisms.