Education and the appropriate clinical interpretation of results are identified challenges for the widespread implementation of fetal aneuploidy screening using cell-free DNA analysis. Some thought leaders propose that positive predictive value (PPV) may be a useful concept for both education and counseling. It is important to recognize that PPV is a statistical measure within the context of a population and that there are limitations to applying it individually. Theoretical PPV and NPV calculations based on estimated pre-test risk and published test performance may provide a foundation for discussion and setting expectations regarding the significance of screening results and may assist patients in decision-making regarding diagnostic testing. However, this information should be interpreted with caution and an understanding of its limitations. Ultimately, all risk assessment must be considered within the broader clinical picture.