The heat-shock protein 90 (Hsp90) is a highly conserved molecular chaperone responsible for correct folding and half-life of target proteins. The Hsp90 interactome is composed of hundreds of client proteins in C. elegans, as an ability to cope under stressful conditions (i.e. environmental challenges, heat, toxicity, pathogen attack). Focusing Hsp90-client interactions not only help understanding of this extensive cytoprotective mechanism, but facilitate efficient chaperone-related therapeutic solutions in age-related, metabolic, neurodegenerative disorders as well as cancer prevention.