Abstract Fifty years ago, people with sickle cell disease (SCD) were discouraged from becoming pregnant, but now, most should be supported if they choose to pursue a pregnancy. They and their providers, however, should be aware of the physiological changes of pregnancy that aggravate SCD and pregnancy’s unique maternal and fetal challenges. Maternal problems can arise from chronic underlying organ dysfunction such as renal disease or pulmonary hypertension; from acute complications of SCD such as acute anemia, vaso-occlusive crises, and acute chest syndrome; and/or from pregnancy-related complications such as preeclampsia, sepsis, severe anemia, thromboembolism, and the need for cesarean delivery. Fetal problems include alloimmunization, opioid exposure, fetal growth restriction, preterm delivery, and stillbirth. Before and during pregnancy, in addition to the assessment and care that every pregnant patient should receive, patients with SCD should be evaluated and treated by a multidisciplinary team with respect to their unique maternal and fetal issues.