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One of the most important indications for guided tissue regeneration (GTR) treatment is class II furcation lesion. However, periodontal regeneration of this type of defect, although possible, is not considered totally predictable, especially in terms of complete bone fill. Many factors may account for variability in the response to regenerative therapy in class II furcation. The purpose of this review is to assess the prognostic significance of factors related to the patient (smoking, stress, diabetes mellitus, acquired immunodeficiency syndrome and other acute and debilitating diseases, and the presence of multiple deep periodontal pockets), local factors (furcal anatomy, defect morphology, thickness of gingival tissue and tooth mobility), surgical treatment (infection control, bone replacement grafts combined with barriers or GTR alone, type of barrier and surgical technique), and postoperative period (plaque control, membrane exposure, membrane retrieval and a regular supportive periodontal care program) for successful of GTR in class II furcations.