The ultimate goal of periodontal therapy is the regeneration of the tissues destroyed as a result of periodontal disease. Currently, two clinical techniques, based on the principles of "guided tissue regeneration" (GTR) or utilization of the biologically active agent "enamel matrix derivative" (EMD), can be used for the regeneration of intrabony and Class II mandibular furcation periodontal defects. In cases where additional support and space-making requirements are necessary, both of these procedures can be combined with a bone replacement graft. There is no evidence that the combined use of GTR and EMD results in superior clinical results compared to the use of each material in isolation. Great variability in clinical outcomes has been reported in relation to the use of both EMD and GTR, and these procedures can be generally considered to be unpredictable. Careful case selection and treatment planning, including consideration of patient, tooth, site and surgical factors, is required in order to optimize the outcomes of treatment. There are limited data available for the clinical effectiveness of other biologically active molecules, such as growth factors and platelet concentrates, and although promising results have been reported, further clinical trials are required in order to confirm their effectiveness. Current active areas of research are centred on tissue engineering and gene therapy strategies which may result in more predictable regenerative outcomes in the future.