Pediatric patients often have poor pregnancy outcomes. Systemic lupus erythematosus predominantly impacts women in their second to fourth decade of life, with childhood-onset disease being particularly aggressive. Reproductive issues are an important clinical consideration for pediatric patients with systemic lupus erythematosus (SLE), as maintaining good disease control and planning a pregnancy are important for maternal and fetal outcomes. In this clinical review, we will consider the safety of medications in managing childhood-onset SLE during conception, pregnancy, and breastfeeding. The developing fetus is at highest risk for teratogenicity from maternal medications during the period of critical organogenesis, which occurs between the first 3-8 weeks following conception. Medications known to be teratogenic, leading to a specific pattern of malformations, include mycophenolic acid, methotrexate, and cyclophosphamide. These should be discontinued prior to a planned pregnancy or as soon as pregnancy is suspected. Hydroxychloroquine is safe and should be continued throughout pregnancy and breastfeeding in those without contraindications to it. Azathioprine and calcineurin inhibitors are felt to be compatible with pregnancy in usual doses and may be used prior to and throughout pregnancy and lactation. Non-fluorinated corticosteroids including methylprednisolone and prednisone are inactivated by the placenta and can be used if needed for maternal indication during gestation. Addition of aspirin may be considered around the 12th week of gestation for prevention of pre-eclampsia. Illustrative cases are presented that demonstrate management of adolescents with childhood-onset SLE through conception, pregnancy, and breastfeeding.