The purpose of the present evidence-based critical review was to define goals and outcomes for regenerative therapy of Class II furcation defects and rank the efficacy of current regenerative procedures based on the available literature. Meta-analysis was employed to quantitate the mean overall expected changes and compare various techniques. The evidence presented in the literature was used to determine factors affecting regeneration of Class II furcation defects. These factors were used to establish decision-making trees to enhance success and highlight potential shortcomings of the technique. Guided tissue regeneration, used alone or in combination with bone replacement grafts, had the highest overall ranking. Mean reduction in probing depths and gains in vertical and horizontal attachment levels were all statistically significant at 6 months. Similar results were obtained in the 12-month studies. Compared to flap debridement, guided tissue regeneration resulted in greater reduction in probing depths and greater gains in vertical and horizontal attachment levels. Guided tissue regeneration provided almost identical results whether used with or without root conditioning, suggesting that root conditioning does not offer an adjunctive effect. A combination of guided tissue regeneration and bone replacement grafts yielded better results than did guided tissue regeneration alone in reducing probing depths and increasing vertical attachment levels. The decision-making trees derived from analysis of these results may assist the clinician in improving success and predictability of guided tissue regeneration procedures in Class II furcation defects.