AbstractMotivated by complex molecular networks of biological organisms, which enable control of the temporal and spatial concentrations of molecules, the bottom‐up development of artificial chemical reaction networks has received renewed interest from biochemists. Based on hybridization and strand‐displacement reactions, DNA‐based chemical reaction networks (D‐CRNs) provide a promising method to describe and analyze (bio)chemical systems, depending on their high programmability and directionality. Herein, progress in the development of D‐CRNs is discussed, and an overview of significant biochemistry applications based on D‐CRNs reported in recent decades is provided. Furthermore, opportunities and future directions for research into D‐CRNs in biochemistry are also discussed.