Nucleic acids play a critical role in life as we know it. It contains the necessary information required for the structure and function of a living organisms. Metal ions play a critical role in stabilizing conformations. In the well-known double helix structure of DNA, metal ions stabilize a particular conformation that ensures storage and propaga-tion of genetic information. Metal ions, however, can interact with various sites on nucleic acids. Moreover, metal coordination can have a tremendous impact on the structure, conformation, stability and the electronic properties of the nucleic acids. The interactions are controlled by the relative affinity of metal ion coordination to the negatively charged phosphodiester backbone versus binding to other donor sites located in the nucleobases. The canonical Watson–Crick base pairs (A-T and G-C) as well as non-canonical base pairs (Hoogsteen and wobble) and mismatched pairs are often sites for metal ion interactions. In this review, an overview will be provided of the structure of different forms of nucleic acids (DNA and RNA) and the impact of different metal ions on their stability and structure. In addition, the recent applications of metal-DNA interactions in nanotechnology, biosensor and bioelectronics will also be discussed along with some therapeutic applications of metal complexes.