Guided Tissue Regeneration (GTR) has become one of the most significant regenerative approaches in periodontology and implant dentistry. Based on the principle of selective cell repopulation, GTR facilitates regeneration of periodontal tissues by preventing epithelial migration into healing defects and allowing periodontal ligament, cementum, and alveolar bone cells to repopulate the wound area. Since its introduction in the early 1980s, GTR has evolved considerably through advances in barrier membranes, bone grafting materials, biologic mediators, tissue engineering, nanotechnology, and regenerative medicine. This review examines the biological principles, materials, clinical applications, advantages, limitations, and future developments of GTR. Contemporary evidence suggests that GTR can predictably improve clinical attachment levels, reduce probing depths, and promote bone regeneration when applied appropriately. Emerging technologies involving stem cells, growth factors, bioactive scaffolds, and three-dimensional bioprinting are expected to further enhance regenerative outcomes in periodontal and peri-implant defects.