Heat shock proteins (HSPs) are molecular chaperones that are involved in protein folding and translocation. During heat shock, both constitutive and stress-inducible HSPs bind to and inhibit irreversible aggregation of denatured protein and facilitate their refolding once normal cellular conditions are re-established. Recent interest in HSPs has been propelled by their association with various human diseases. Amphibian model systems, as shown in this review, have had a significant impact on our understanding of hsp gene expression and function. Some amphibian hsp genes are expressed constitutively during oogenesis and embryogenesis, while others are developmentally regulated and enriched in selected tissues in a stress-inducible fashion. For example, while hsp70 genes are heat-inducible after the midblastula stage, hsp30 genes are not inducible until late neurula/early tailbud. This particular phenomenon is likely controlled by chromatin structure. Also, hsp genes are expressed during regeneration, primarily in response to wounding-associated trauma. The availability of amphibian cultured cells has enabled the analysis of hsp gene expression induced by different stresses (e.g. cadmium, arsenite, proteasome inhibitors etc.), HSP intracellular localization, and their involvement in stress resistance. Furthermore, hyperthermia treatment of adult amphibians reveals that certain tissues were more sensitive than others in terms of hsp gene expression. Finally, this review details the evidence available for the role of amphibian small HSPs as molecular chaperones.