The so called Heat-shock proteins (Hsp) are the product of different genes induced by a sudden and/or short-lasting temperature elevation. However, the term Hsp is generally used with great flexibility to indicate proteins induced also by other stressors besides heat shock. Many Hsp are also chaperones since they assist nascent polypeptides to fold correctly. Other canonical functions of chaperones include, in addition to protein folding, assisting protein refolding and translocation through membranes, ushering proteins damaged beyond repair to degradation, and dissolution of protein aggregates. Hsp play a key role in various human chronic diseases such as cancer, neurodegenerative diseases, cardiovascular diseases, diabetes and in acute injury (i.e. trauma). Furthermore, Hsps may be used as possible circulating biomarkers helpig the clinicians for diagnosis, prognosis and treatment. In the present review we focus our attention on the possible role and different clinical significance of two important heat shock proteins (i.e. heme oxygenase-1 and Hsp70) in traumatic injury.