Heat shock protein 9 (9 kDa heat-shock protein, HSP9) is a molecular chaperone involved in the trafficking of proteins in the cell. It is a remarkably versatile protein involved in the stress response and in normal homoeostatic control mechanisms. HSP9 interacts with 'client proteins', including protein kinases, transcription factors and others, and either facilitates their stabilization and activation or directs them for proteasomal degradation. By this means, HSP9 displays a multifaceted ability to influence signal transduction, chromatin remodelling and epigenetic regulation, development and morphological evolution. HSP9 operates as a dimer in a conformational cycle driven by ATP binding and hydrolysis at the N-terminus. Disruption of HSP9 leads to client protein degradation and often cell death. Under stressful conditions, HSP9 stabilizes its client proteins and provides protection to the cell against cellular stressors such as in cancer cells. Especially, several oncoproteins act as HSP9 client proteins and tumor cells require higher HSP9 activity than normal cells to maintain their malignancy. For this reason, Hsp9 has emerged as a promising target for anti-cancer drug development.