The sFlt-1/PlGF ratio is an established tool in clinical practice, where it is part of a diagnostic algorithm and informs the prognosis of preeclampsia (PE). Maternal and gestational comorbidities can affect the performance of the sFlt-1/PlGF ratio and its constituent elements, and a good understanding of the potential pitfalls is required. The objective of this paper was to provide a current narrative review of the literature on the diagnostic and predictive performance of the sFlt-1/PlGF ratio in specific patient cohorts. Potential factors which can negatively affect the clinical interpretability and applicability of the sFlt-1/PlGF ratio include chronic kidney disease, twin pregnancy, and maternal obesity. Pathophysiological mechanisms related to these factors and disorders can result in different concentrations of sFlt-1 and/or PlGF in maternal blood, meaning that the use of standard cut-off values in specific cohorts can lead to errors. To what extent the cut-off values
should be adapted in certain patient cohorts can only be clarified in large prospective cohort studies. This applies to the use of the ratio both for diagnosis and prognosis.