In this review, we discuss the heat shock response, a specific example of gene expression that has been studied over the past 25 years, and its relevance to acute lung injury and other critical conditions. The heat shock response has been observed in virtually all organisms and involves the rapid induction of a set of highly conserved genes that encode heat shock proteins (HSPs). The HSP70 family represents the most prominent eukaryotic group of HSPs. It has been suggested that members of the HSP70 family act in the protection of cellular damage by binding to denatured or abnormal proteins after heat shock, thereby preventing protein aggregation. The capacity of HSPs to subserve cytoprotection has produced considerable interest from the perspective of elucidating the pathophysiology of organ damage and dysfunction. Several studies support the hypothesis that HSPs are cytoprotective In addition, recent investigations have demonstrated that HSP70 is released into the systemic circulation and is involved in the activation of innate immunity.