The small HSP27 is an actin-specific molecular chaperone involved in cytoskeleton architecture, cell migration, metabolism, survival, growth/differentiation, mRNA stabilization, and tumor progression. HSP27 is detected in nearly all cells with different expression levels. A variety of stimuli induce expression and/or phosphorylation of HSP27. HSP27 phosphorylation affects some of its cellular functions as phosphorylation affects HSP27 oligomerization, which in turn has an impact on some of HSP27 functions. HSP27 has been involved in different kidney diseases playing protective and counter-protective roles. HSP27 shows a protective role against several stressors as reactive oxygen species, hypoxia, osmotic stressors, etc. HSP27 and phospho-HSP27 protein levels are increased in stressed and diseased cells.  The current review presents HSP27 in the pathogenesis of different kidney diseases as renal injury, fibrosis and renal cell carcinoma, highlights its role as a potential biomarker and offers new therapeutic optionsthrough manipulation of HSP27.