D2O and H2O, as two important solvents with very similar properties, play a pivotal role in nuclear industrial production, life and scientific research. Unfortunately, D2O and H2O are highly susceptible to contamination by each other, so effective qualitative and quantitative analysis of both is necessary. This review comprehensively discusses the progress in optical sensing for the detection of trace amount of H2O in heavy water or vice versa, mainly including five types of analytical systems: inorganic nanocrystals, carbon-based nanomaterials, lanthanide complexes, organic polymers, and organic small molecules. The whole article is divided into several sub-sections based on multiple mechanisms underlying the design of heavy water optical sensors, i.e., the difference in binding energy, the difference in quenching efficacy of oscillator types and the difference in acid-base of H2O and D2O. The working mechanism, advantages and disadvantages, analytical performance and applications of the reported sensors in recent years were analyzed in detail, and the future development is envisioned for the optical sensors towards distinguishing D2O and H2O.