The periodontal ligament is connective tissue located between the cementum of the teeth and the alveolar bone of the mandibula. It plays an integral role in the maintenance and regeneration of periodontal tissue. Fibroblasts are the responsible for maintaining this tissue. They can be either multipotent or composed of heterogeneous cell populations that differ in their function. Despite the similar morphology with gingival fibroblasts, periodontal ligament fibroblasts (PLF) appear to display distinct functional activities in the maintenance of tissue integrity. PLF produce osteoblast-related extracellular matrix proteins and show higher alkaline phosphatase activity compared with gingival fibroblasts. Human Periodontal Ligament Fibroblasts actively participate in immune and inflammatory events in periodontal disease, such as periodontitis.