Heat shock proteins (HSP) or stress proteins are produced by prokaryotic and eukaryotic cells in response to a variety of environmental stressors. The heat shock response is one of the most universal reactions known and heat shock proteins are among the most conserved molecules in phylogeny. Recent findings concerning the immune response to heat shock proteins are discussed especially with respect to the role of HSPs postulated in septic disease and inflammation, in antipathogenic immunity and in the induction of autoimmune diseases. Results and speculations considering a relationship between HSPs and gamma/delta T cells or polyreactive antibodies, possibly as part of a phylogenetic old immune system, are critically reviewed.