Fibroblasts are mesenchymal cells which perform many vital functions during development and in adulthood. They are responsible for much of the synthesis of extracellular matrix in connective tissue. They also play major roles in wound healing. Many diseases comprise fibroblasts, either because fibroblasts are related in their etiology or because of the fibrosis that accompanies damage to other cell types. Human oral fibroblasts (HOrF), located in the oral cavity, have the ability to rapidly repair defects in the oral cavity. HOrF, in contrast to skin fibroblasts, can more quickly reorganize the extracellular matrix and migrate for wound repair. Abnormal proliferation of HOrF can lead to the development of oral squamous cell carcinoma. HOrF are a useful model for elucidating the mechanisms of fibrosis and developing treatments for oral cancers.