Furcation involvement (FI) is one of the most detrimental factors affecting tooth survival rate over time. Several authors have used the severity of FI for assessing the prognosis of the tooth and the complexity of periodontal disease. While many approaches have been shown to improve the prognosis of furcation-involved teeth, clinical guidelines recommending one treatment or another (based on the horizontal and vertical component of the furcation defects) have not yet been proposed. To this aim, the present article introduces recommendations for the treatment of molars with FI and discusses different treatment options with their potential regenerative approaches. Patient-related factors, together with hard and soft-tissue conditions that may affect the outcomes of periodontal regeneration, are discussed.