Hemolytic disease of the newborn (HDN) occurs due to maternal IgG antibodies crossing the placenta thereby producing hemolysis mainly due to Rh, ABO and Kell groups. A systematic approach to the Rh HDN involves an obstetric history of previous isoimmunized baby, timing and regular monitoring of maternal Rh antibodies and pigment assay of amniotic fluid. Timely decision regarding in utero transfusion and early termination of pregnancy based on the maternal monitoring has radically improved the outcome of these babies. Antenatal prophylaxis with anti D has resulted in great reduction in the magnitude of Rh problem. The fetal blood sampling and in-utero intravenous transfusions has made it possible for almost 100% survival of isoimmunized pregnancies without hydrops. Alternative methods--IVIG and plasma exchange are still of limited application. ABO HDN though common is not a serious form of disease and dose not warrants invasive antenatal monitoring. Anti-Kell is found in patients having received multiple transfusions and the rapid progress of hemolysis in them may not allow such systematic follow up as in Rh HDN.