Neonatal lupus, although quite rare, carries a significant mortality and morbidity when the fetal heart is the targeted organ. Anti-SSA/Ro-SSB/La antibodies are present in more than 85% of mothers whose fetuses are identified with congenital heart block (CHB) in a structurally normal heart, but the risk for a woman who has the candidate antibodies to have a child who has CHB is approximately 2%. Although the precise pathogenic mechanism of injury remains unknown, it is clear that the antibodies alone are insufficient to cause disease, and fetal factors are likely contributory. In vivo and in vitro evidence supports a pathologic cascade, involving apoptosis of cardiocytes, surface translocation of Ro and La antigens, binding of maternal autoantibodies, secretion of profibrosing factors (eg, tumor growth factor ) from the scavenging macrophages, and modulation of cardiac fibroblasts to a myofibroblast-scarring phenotype. The spectrum of cardiac abnormalities encompasses varying degrees of block identified in utero and late-onset cardiomyopathy. Better echocardiographic measurements that identify first-degree block in utero may be the optimal approach for pregnant women at risk; prophylactic therapies, including treatment with intravenous immunoglobulin, await larger trials.