Fibroblasts are found in most tissues of the body. They exhibit several phenotypes including non-contractile fibroblasts, contractile myofibroblasts, and intermediate phenotypes including the protomyofibroblast. Fibroblasts are metabolically active cells which play critical roles regulating extracellular matrices, interstitial fluid volume and pressure, and wound healing. Fibroblast numbers can be maintained or expanded by proliferation of resident populations but in addition, recent evidence indicates they can also be derived through epithelial-mesenchymal transition or from circulating and tissue-derived mesenchymal stem cells. Many diseases are associated with dysregulation of the injury repair response and fibroblast function, leading to increased or decreased deposition of extracellular matrix proteins, altered tissue architecture, impaired function and in some cases significant morbidity and mortality. There are currently no specific therapies that target fibroblast-associated pathology but increasing knowledge of pathological mechanisms has led to development of new agents providing hope for improved treatment of these diseases.