The midkine (MK) family consists of only two members, namely MK and pleiotrophin (PTN). MK and PTN share receptors and biophysical characteristics, such as a heparin-binding property. MK and PTN exert several biological activities, which include fibrinolytic, anti-apoptotic, mitogenic, transforming, angiogenic, and chemotactic ones. These activities suggest that these growth factors are involved in carcinogenesis. Indeed, strong expression of MK and PTN in human carcinomas, and the anti-tumor activity of antisense oligonucleotides for MK and ribozymes for PTN further support their importance in cancer. In addition, MK plays critical roles in the pathogeneses of various disorders involving inflammation such as reperfusion- and cisplatin-induced renal dysfunction and vascular restenosis after angioplasty. MK antisense oligonucleotide ameliorates these disorders. Zebrafish and Xenopus MK can induce neural tissues. MK and PTN are localized in the radial glial processes of the embryonic brain, and are induced in reactive astrocytes by ischemic insults. I summarize here the biological significance of the MK family in cancer, inflammation and neural development.