The lack of predictive value in periodontal disease detection has stimulated intense research efforts in the development of diagnostic tests. Present methodology using periodontal probes or radiographs to determine disease susceptibility fails to allow an accurate periodontal risk assessment. The analysis of gingival crevicular fluid components offers great potential as a source of factors that may be involved in active periodontal bone loss. Over the past decade investigators have begun to identify several molecules associated with active periodontal tissue destruction. Recent advances in orthopedics and osteoporosis have provided new biochemical markers of bone resorption, including oral bone loss. The development of new diagnostic test strategies that target the analysis of bone-specific markers offers great promise to accurately assess active disease.