Conjugation with artificial nucleic acids allows proteins to be modified with a synthetically accessible, robust tag. This attachment is addressable in a highly specific manner by means of molecular recognition events, such as Watson–Crick hybridization. Such DNA–protein conjugates, with their combined properties, have a broad range of applications, such as in high-performance biomedical diagnostic assays, fundamental research on molecular recognition, and the synthesis of DNA nanostructures. This Review surveys current approaches to generate DNA–protein conjugates as well as recent advances in their applications. For example, DNA–protein conjugates have been assembled into model systems for the investigation of catalytic cascade reactions and light-harvesting devices. Such hybrid conjugates are also used for the biofunctionalization of planar surfaces for micro- and nanoarrays, and for decorating inorganic nanoparticles to enable applications in sensing, materials science, and catalysis.