Ping Li, Xu Wang, Jian Wei, Huaibin Jiang, Yang’en You
Deuterium labeling is invaluable in life sciences and pharmacy, enhancing drug stability and efficacy. Beyond pharmaceuticals, deuterium compounds advance materials science through improved optical and electronic material properties. In chemical research, they enable reaction mechanism studies and interference‐free NMR spectroscopy. These applications highlight deuterium chemistry's essential role across scientific fields. Among deuterium sources, deuterium oxide (D 2 O) is widely recognized for its cost‐effectiveness, stability, and versatility in various reactions. This review explores the use of D 2 O as a deuterium source across key reaction types, including hydrogen isotope exchange, reductive deuteration, and defunctionalization–deuteration. Detailed insights into reaction mechanisms, catalyst selection, and experimental conditions are provided. Furthermore, the review highlights the advantages of D 2 O in achieving selectivity and compatibility in diverse chemical environments, addressing key challenges in deuterium chemistry. Finally, future directions and emerging trends in optimizing D 2 O‐based deuteration methods are discussed.