The periodontal ligament, located between the cementum and the alveolar bone, has a width ranging from 0.15 to 0.38 mm. Regeneration and homeostasis of the periodontal ligament are highly significant functions in relation to periodontal therapy, tooth transplantation or replantation, and orthodontic tooth movement. The purpose of this review is to discuss the regulatory mechanisms of regenerative and homeostatic functions in the periodontal ligament based on currently published studies and also on our own experimental data. We consider the capability of the ligament tissue to promote or to suppress calcification in connection with bone and cementum formation and the maintenance of the periodontal ligament space. Also discussed are the involvement of the periodontal ligament tissue in the regenerative ability, cell proliferation, growth and differentiation factors, extracellular matrix proteins, homeostatic phenomena, function of Malassez epithelial rests, tooth movement, or occlusal loading. Regulatory mechanisms for regeneration and homeostasis of the periodontal ligament are hypothetically proposed.