The cytokine hepatocyte growth factor (HGF) and its receptor c-Met are a ligand-receptor pair with important functions in a communicative interplay between HGF-producing, mesenchymal cells and c-Met-expressing target cells. HGF is cytoprotective and causes regeneration of parenchyma after tissue damage in several organs. The receptor c-Met was first characterized as an oncogene product being responsible for the transformation of an osteosarcoma cell line. HGF or c-Met is overexpressed in several human cancers, including various carcinomas. Some cells of hematopoietic origin also seem to be capable of c-Met expression, but the precise role of HGF in normal hematopoiesis is yet to be determined. In blood malignancies like acute myelogenous leukemia and, notably, multiple myeloma, HGF is overproduced and has implications for the prognosis of the patients. Biological significance of HGF overexpression in multiple myeloma is discussed and is likely to include effects on bone turnover and angiogenesis.