Landmark trials impact how we care for patients. These studies often have convincing data that lead to new or updated practice guidelines by professional societies and other organizations. In this review, we present four such studies of maternal interventions that defined standards of care and continue to influence what we do today. The first found that the rate of perinatal HIV transmission was reduced in women with HIV in pregnancy with treatment of zidovudine in the antepartum, intrapartum, and neonatal periods. The second found that postoperative infections and use of resources were reduced in women who received a single intravenous dose of azithromycin in addition to their standard preoperative antibiotics for cesarean delivery. The third study did not find any benefit in treating subclinical hypothyroidism or hypothyroxinemia in pregnancy preventing routine use of levothyroxine for these patients. The fourth showed that the treatment of non-severe chronic hypertension in pregnancy safely resulted in improved pregnancy outcomes.