An assembly of systemic and metabolic changes that occur within 90 minutes after the onset of a systemic inflammatory reaction is termed as acute phase reaction/response. This is caused due to the change in the concentrations (increase/decrease) of a class of proteins called as acute phase proteins. In periodontitis, subgingival gram negative bacteria release endotoxins that interact with Toll-like receptors, expressed on polymorphonuclear leucocytes and monocytes resulting in the formation of a complex that activates the immune system. This results in a cascade of inflammatory changes resulting in the production of acute phase proteins by the pro-inflammatory cytokines and glucocorticoid hormones. Recent studies have shown increased levels of acutephase proteins with gingival inflammation, including experimental gingivitis and periodontitis reflecting the locally stressed environment. New acute-phase phenomena continue to be recognized, and the mechanisms mediating them are becoming better understood. This article therefore highlights about the vital acute phase proteins and their association with periodontal diseases.