Over the past 30 years, many advancements have been made regarding defect regeneration by means of biologics, membranes, and bone grafting materials. More recently, however, substantial evidence appears to indicate that certain combinations of regenerative materials may additionally improve the clinical outcomes, in defects with a complicated anatomy (eg, growth factors with bone grafting materials, growth factors with barrier membranes, bone grafting materials with barrier membranes). The aim of this chapter is to analyze the multitude of clinical studies on the topic and decipher which combinations have been clinically more successful for the regeneration of periodontal tissues. Available data indicate that the follwing combina tion approaches have been een histologically shown bwn to promote periodontal regeneration in humans: bone grafting material with enamel matrix, erivative (Emy),,bone material with growth differentiaoni factor (GDF-5), and (4) bone grafting' material'with barrier over, favoring the combined use of biologics and bone grafting materials.