In transfusion medicine and clinical immunology, cell-free fetal DNA (cffDNA) is analysed from maternal plasma of pregnant women to predict fetal blood groups with the purpose of (1) assessing the risk of haemolytic disease of the fetus and newborn (HDFN) in immunized women and (2) guiding targeted Rh prophylaxis in non-immunized RhD-negative women. National programmes for guiding prophylaxis are now implemented in around 6-7 European countries; assay accuracy is very high, with sensitivities of 99Á9%. Sensitivity is challenged by low quantities of cffDNA, especially in early pregnancy. Specificity is challenged by the polymorphic Rh blood group system, where careful attention is needed to navigate among the many RHD variants that may complicate cffDNA analysis and interpretation of results, especially in populations with mixed ethnicities. However, fetal RHD testing is feasible when implemented with careful attention to these issues. The success of predicting fetal RhD and its successful clinical implementation should encourage widespread implementation. For blood groups that are determined by SNPs, such as KEL or Rhc, novel techniques such as next-generation sequencing and droplet digital PCR are now providing accurate non-invasive prediction of these fetal blood groups. Future work on non-invasive prenatal testing of fetal blood groups determined by SNPs may consolidate the application for cell-free DNA testing for such targets. At ISBT, the newly formed cfDNA subgroup of the Red Cell Immunogenetics and Blood Group Terminology Working Party will work to facilitate clinical applications, implementation and evaluation of cell-free DNA testing.