Rh-isoimmunization is the most common cause of fetal anemia. The problem of Rh-isoimmunization has been the most challenging and yet intrauterine transfusion for fetal anemia, the most rewarding therapy in fetal medicine. Despite national recommendations and standard protocols for RhD immune prophylaxis, the incidence still remains high. This Focus aims to cover all aspects of Rh-isoimmunization in a brief and concise manner and easy-to-comprehend flow of topics with emphasis on Prophylaxis, Investigation and Treatment algorithms. It also covers the neonatal aspects of the affected fetuses, their potential long-term outcomes, and issues such as recurrent hydrops which can be clinically challenging. The promising and potential role of noninvasive prenatal testing and the newer treatment methods have also been discussed.