The ultimate goal of periodontal regeneration is to restore the damaged alveolar bone proper, root cementum, and periodontal ligament with collagen fibers inserted into the root surface. The search for new regenerative strategies is a challenging field of periodontal research, and tissue engineering, using stem cells, has recently been shown as a promising approach. This paper aims at reviewing the current available literature on the use of stem cells for the treatment of periodontitis. Up to now, different mesenchymal stem cells (MSCs) have shown potential for periodontal regeneration in animal studies. The most investigated MSCs for periodontal regeneration are bone marrow MSCs (BMMSCs), periodontal ligament stem cells (PDLSCs), and dental pulp stem cells (DPSCs), which have shown very promising results in animal models. Few studies on humans are available but BMMSCs, PDLSCs, and DPSCs have been proven safe and effective. Clinical trials are sparse, but tend to support the efficacy of MSCs for periodontal regeneration. In the future, more human studies will be required to support the use of MSCs in daily clinical practice, especially in order to identify the best protocol to harvest, process, and graft MSCs. Future perspectives include trans-differentiation of somatic cells to generate induced pluripotent stem cells, homing procedures, the use of exogenous stem cells, and 3D-printed scaffolds.