Cellular stress is present during tumour development. Stressed cells in most tissues increase the production of ‘molecular chaperones’ - proteins that maintain the conformation and function of client substrates. Upregulated chaperone levels constitute an adaptive response that enhances cell survival. Tumour cells display constitutively-elevated levels of molecular chaperones, probably reflecting efforts at maintaining homeostasis in a hostile environment. The molecular chaperone HSP90 is unique - its protein clients are primarily involved in cellular proliferation. Nuclear receptors (NR) are signaling molecules and HSP90 clients whose aberrant activity is widely implicated in oncogenesis. It is currently unknown if stress-induced chaperone overexpression influences NR activity and potentially cancer progression. It is also possible that stress alters NR ligand specificity. These agonists, antagonists or ‘selective nuclear receptor modulators’ modulate NR activity in cancer chemotherapy. Understanding chaperone influence on NR signaling should facilitate the design of patient-specific treatment strategies.