Hepatocyte growth factor/Scatter factor (HGF/SF) which was initially discovered as a mitogen of mature hepatocyte in the serum of patients with fulminant hepatic failure, was purified from plasma of their patients and cloned cDNA for the factor. An identical protein termed scatter factor (SF) and tumor cytotoxic factor was subsequently purified. The actions  of HGF/SF are mediated via a single receptor c-Met, the  product of the c-met proto-oncogene, encoding an intracellular tyrosine-kinase domain, expressed on  both epithelial and endothelial cells. Thus, HGF/SF is now recognized as a broad-spectrum and multifunctional cytokine that exhibits various biological activities; (i) mitogenic activity for epithelial cells, vascular endothelial cells, (ii) cytotoxic  activity  to certain tumor cells, (iii) motogenic activity (dissociation of epithelial cell colonies in monolayer cultures) (iv) morphogenic activity in developmental stage.  HGF/SF  is first synthesized and secreted as an inactive single-chain precursor (pro-HGF) in certain mesenchymal cells, and then activated to a heterodimeric form (mature HGF) consisting of a heavy chain (60 kDA) and a light chain (30 kDA) by serine proteases such as HGF activator (HGFA), urokinase, tissue plasminogen activator (t-PA) and coagulation factor XII. The heavy chain has N-terminal heparin binding heparin loop, four kringle structures, and the light chain has serine protease like domain . Several truncated variant proteins of HGF/SF by alternative splicing were reported. From several reports, HGF/SF is a potentially therapeutic substance for patients with fulminant hepatic failure, liver cirrhosis and lung fibrosis and so on,. In this review, the structure, functions and the structure-function relationship  of  HGF/SF will be presented, along with a discussion of its physiological roles in normal and pathological conditions, and possibility of therapeutic usage  of HGF/SF.