Periodontal diseases present with a wide range of clinical variability and severity. Individual susceptibility seems to be of major importance in determining the manifestation and progression of the disease. A better understanding of the molecular mechanisms of action of the immune system is of paramount importance to our ability to prevent and treat occurrence and recurrence of periodontal diseases. Recent advances in immunobiology are very promising for the identification of special categories of patients at risk for periodontal breakdown. This review discusses the most recent studies in this field and the possible clinical applications of recent advances.