The Present study is a literature review about fibroblasts (fs) of periodontium that are the dominant cell types of the connective tissue in the body.An emerging concept is that fs are not hemogenous and can be separated in to subsets, on the basis of morphology, size, collagen subtype and their tissue localization. (Gingiva, PDL Or Granulation tissue (Gt)) For example myofibroblasts in Gt distinguished from other fs by their expression of desmin (a smooth muscle actin). They becoming contractile and thus promoting closure of wound.CD40 is a transmisable protein which some of fs display its expression especially in inflammation. It may interact with CD40 ligand on the other cells and activate secretion of cytokines. Thus by blocking this interaction could diminish damage of periodontal inflammation.Gingival Fs have the ability to produce cytokines like IL1b, IL-6, IL-8 and PGE2 in response to lipopolysaccharide (LPS) of microorganisms. This finding confirm the notion GFs function as accesory immune cells growth factors such as EGF, PDGF and TGFPl activate synthesis of collagen by Fs.Except intrinsic mediators, extrinsic factors as drugs or nicotine stimulate Fs. Nicotine prevents of fs proliferation. Nifedipine promotes collagen synthesis by Fs and induce gingival enlargement. But in here ditary gingival fibromatosis increased proliferation of fs, fibronectin and collagen contribute to clinical enlargement.