Recently, natural DNA has emerged as an appealing biomacromolecule for functional materials. It is abundant and renewable, and possesses the well known double helix structure that promises many unique properties difficult to find in other polymers. Natural DNA has been applied in electronic, optical and biomaterials, as a catalyst for enantioselective reactions, and as a material for cleaning the environment. Most of the applications are based on combining DNA with other chemicals or nanoparticles by electrostatic binding, intercalation or groove binding. In this critical review article, recent developments in utilizing natural DNA are reviewed by focusing on three basic properties of DNA: the electrostatic property as a polyelectrolyte, selective affinity for small molecules, and biocompatibility (128 references).