The rhesus blood type was first discovered in 1937 by Karl Landsteiner, Alexander S Wiener and Levine and associates confirmed in 1941 that erythroblastosis was due to maternal isoimmunization against paternally inherited fetal factors Ronald Finn, in Liverpool, England applied a microscopic technique for detecting fetal cells in the mother’s blood. In spite of availability of anti-D for prevention of Rh-isoimmunization, it is still prevalent in 0.8–1.5% of pregnancy. This chapter covers the pathophysiology, prevention, and investigations.