Midkine is a heparin-binding cytokine or a growth factor with a molecular weight of 13 kDa, and is rich in both basic amino acids and cysteine. Here, I summarize general information on midkine. Midkine binds to oversulfated structures in heparan sulfate and chondroitin sulfate. The midkine receptor is a molecular complex containing proteoglycans and transmembrane proteins such as low density lipoprotein receptor-related protein and integrins. Receptor-like protein tyrosine phosphatase-zeta is a chondroitin sulfate proteglycan and serves as the key receptor component in the majority of cases. Intracellular tyrosine phosphorylation is increased as the result of midkine action. Midkine promotes migration, survival and other activities of target cells. Midkine has about 50% sequence identity with pleiotrophin. Mice deficient in both factors exhibit severe abnormalities including female infertility and developmental deficits. In adults, midkine is expressed in damaged tissues and involved in the reparative process. It is also involved in inflammatory reactions by promoting the migration of inflammatory leukocytes, induction of chemokines and suppression of regulatory T cells. Midkine is expressed in a variety of malignant tumors and promotes their growth and invasion. Midkine appears to be helpful for the treatment of injuries in the heart, brain, spinal cord and retina. Midkine inhibitors (siRNAs, antisense oligoDNAs, aptamers, antibodies, peptides, low molecular weight compounds etc) are expected to be effective in the treatment of malignancies, rheumatoid arthritis, multiple sclerosis, renal diseases, restenosis, hypertension and adhesion after surgery. Midkine is an interesting molecule upon investigating pathogenesis and therapy of various diseases.