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Summary:The pathogenesis of Dupuytren’s disease (DD) remains unclear although there is increasing evidence supporting the role of stem cells in this and other fibrotic conditions. This review examines the role of DD tissue-associated embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs), and circulating fibrocytes and circulating MSCs, in the biology of DD. It is exciting to infer that dysfunction of an upstream ESC-like population within the affected tissue leads to the downstream development and proliferation of aberrant myofibroblasts through a putative MSC intermediate. This ESC-like population may be a potential novel therapeutic target through modulation of the renin-angiotensin system. Furthermore, circulating CD34+ fibrocytes and MSCs either derived from the bone marrow, peripheral blood cells, or DD-associated ESC-like population, may serve as potential additional extra-palmar reservoirs that undergo endothelial-to-mesenchymal transition, eventually giving rise to the aberrant myofibroblasts. Further studies examining the relative roles of these stem cells and the precise regulatory pathways that govern them may lead to novel therapy that targets these populations.