The pioneering studies carried out on heat shock-induced synthesis of specific proteins in the early 1970s did not identify any Hsp60 family protein in Drosophila. By the early 1980s, although the members of Hsp60 family of heat shock proteins (Hsp) were identified in a wide range of eukaryotes as homologs of the bacterial GroEL, none was known in Drosophila. The existence of the Hsp60 family protein was serendipitously revealed in Drosophila in my laboratory in 1989. Contrary to the earlier reports that all tissues in flies display the canonical heat shock response, the larval Malpighian tubules (MT) did not show induction of any of the major Hsps but synthesis of a putative Hsp60 family protein was found to be the most abundant in this tissue. A few years later, we identified this MTspecific heat shock-induced protein to indeed be a member of the Hsp60/chaperonin family. The Drosophila genome sequence projectssubsequently revealed four putative Hsp60 gene sequences in the D. melanogaster genome. The present historical perspective chroniclescontributions from my and other laboratories that unraveled several aspects of intriguing biology of the multiple Hsp60 genes in D. melanogaster, and highlights challenging questions awaiting future studies.