Metal-mediated base pairs represent an elegant way for the site-specific functionalisation of nucleic acids. In this type of base pair, the hydrogen bonds between complementary nucleobases are replaced formally by coordinative bonds to one or more transition-metal ions. This Review presents an overview of metal-mediated base pairs reported so far. It gives an insight into the characterisation of metal-mediated base pairs and into the structures of the resulting metal-modified nucleic acids. In addition, a summary of applications exploiting the formation of metal-mediated base pairs is presented. The applications include, for example, metal-ion sensors of various types, a protein sensor, and DNA-based molecular machines. Initial reports on the potential use of metal-mediated base pairs in the context of charge transfer through nucleic acid double helices are summarised as well.