Background &amp; Aims <p>Enhancing water use efficiency (WUE) is critical in the regulation of water stress in plants. Since both WUE and ¹³C discrimination depend on stomatal conductance (<i>gₛ</i>) and CO₂ assimilation rate (<i>A</i>), Δ¹³C values have been widely utilized as a proxy for WUE. However, to distinguish whether changes in WUE are attributable to variations in <i>A</i> or <i>gₛ</i>, δ¹⁸O values are increasingly incorporated into the analysis. In this review, we aim to analyze the advantages and limitations of this dual isotopic model for identifying the drivers of changes in plant WUE.</p> Methods <p>We conducted a literature review to examine the factors governing the correlation between WUE and isotopic values. Additionally, we collate existing studies to discuss where the dual isotope model offers valuable insights into changes in WUE and where it reaches its limits.</p> Results <p>While previous studies on trees revealed that the dual-isotope model effectively identified the relationship of WUE to climatic factors, WUE in crops is additionally controlled by plant group characteristics and fertilization effects. These determining factors can also be identified through the application of the dual isotope model, however, under conditions of low vapor pressure deficit, the applicability of the dual isotope model appears to be limited.</p> Conclusion <p>The dual isotope model holds significant potential for elucidating the mechanisms controlling WUE. This is particularly relevant for crops, as it facilitates the identification of cultivars and soil management practices that ensure high biomass production, even under conditions where gₛ is reduced due to water stress.</p>