RhD blood group incompatibility between a pregnant woman and her fetus can result in maternal alloimmunization and consequent haemolytic disease of the newborn (HDN) in subsequent pregnancies. The D-negative blood group is found in 15% of whites, 3-5% of black Africans, and is rare in Asians. Recent technological advances in non-invasive prenatal determination of the fetal RHD status using cell-free fetal DNA (cffDNA) have opened new avenues for the management of D-negative pregnant women. In this review applications for the high risk women, as well as potential for routine screening will be discussed. The use of non-invasive prenatal diagnosis and the management of other blood incompatibilities will also be discussed.