This review summarizes the data which relate the validation and application of host response markers as diagnostic tests for periodontal diseases. Practical considerations regarding the general application and evaluation of a diagnostic test for periodontal disease are presented. Experiments which have documented the performance of host response markers as diagnostic measures of disease activity in terms of sensitivity, specificity, and predictive values are summarized. Particular emphasis is placed on the diagnostic potential of gingival crevicular fluid (GCF) components. The considerable body of evidence supporting the potential application of GCF-PGE2 levels for predicting episodes of disease progression and reflecting disease activity is summarized and placed into perspective for the development of future diagnostic tools.