Biochemical experiments over the past 40 years have shown that nucleoside diphosphate (NDP) kinase activity, which catalyzes phosphoryl transfer from a nucleoside triphosphate to a nucleoside diphosphate, is ubiquitously found in organisms from bacteria to human. Over the past 10 years, eight human genes of the nm23/NDP kinase family have been discovered that can be separated into two groups based on analysis of their sequences. In addition to catalysis, which may not be exhibited by all isoforms, evidence for regulatory roles has come recently from the discovery of the genes nm23 and awd, which encode NDP kinases and are involved in tumor metastasis and Drosophila development, respectively. Current work shows that the human NDP kinase genes are differentially expressed in tissues and that their products are targeted to different subcellular locations. This suggests that Nm23/NDP kinases possess different, but specific, functions within the cell, depending on their localization. The roles of NDP kinases in metabolic pathways and nucleic acid synthesis are discussed.