The lack of precise clinical criteria for assessment of periodontal disease has led to a search for alternative means of determining active disease sites, prognosis of future sites of breakdown, and response to therapy. This review highlights the potential array of biomarkers present in gingival crevicular fluid and which may relate to existing or predicted tissue regions undergoing metabolic change and derived from bacterial or host-cell-derived products. Among the former may be listed endotoxin, amines, butyrate, and a variety of enzymes and their inhibitors, such as trypsin-like proteases and bacterial collagenase. Arising from host cells is a variety of leucocytic hydrolase enzymes, lactoferrin, and lysozyme. These appear to be useful inflammatory markers and may be distinguished from products of connective tissue breakdown which include collagenous and non-collagenous products, including collagen peptides, osteonectin, and fibronectin. The proteoglycans have found particular favor as biomarkers of possible bone-resorptive activity. Attention has also been directed at the immune response, including comment on immunoglobulins, complement, eicosanoids, and cytokines. This review lists available information on the presence of these in gingival sulcus fluid and wherever possible relates their presence to disease activity.