- Introduction: Chronic fibrotic disorders are challenging clinical problems. The major challenge is the identification of specific targets expressed selectively in fibrotic tissues. Collagen accumulation is the hallmark fibrosis. HSP47 is a collagen-specific chaperon with critical role in collagen folding. This review discusses the anti-fibrotic potential of HSP47. Areas covered: This review compiles data retrieved from the PubMed database with keywords 'HSP47+fibrosis' from 01/2005 to 06/2020. We examined 1) collagen biology and its role in fibrotic diseases, 2) HSP47 role in fibrosis, 3) HSP47 inhibition strategies and 4) clinical investigations. The identification of the HSP47-collagen binding site led to the development of methods to screen HSP47 inhibitors with anti-fibrotic potential. Specific in vivo delivery systems of HSP47 siRNA to fibrotic tissue reduced collagen production/secretion associated with fibrosis inhibition in preclinical models. This strategy is about to be tested in clinical trials. Expert opinion: As a collagen-specific chaperon, HSP47 is a promising therapeutic target in fibrosis. Preclinical models have shown encouraging anti-fibrotic results. Anti-HSP47 strategies need to be further evaluated in clinical trials. The increase in circulating-HSP47 in lung fibrosis patients highlights the potential of HSP47 as a noninvasive biomarker and may represent an important step toward personalized medicine in fibrotic disorders.