Significant advances in strategies to prevent perinatal human immunodeficiency virus (HIV) infection have resulted in major declines in new diagnoses in the United States, however, new diagnoses continue to occur. When these transmissions happen, it is usually a result of a breakdown in the delicate prevention cascade which includes the spectrum from HIV testing of individuals of childbearing age to antiretroviral therapy (ART) for pregnant individuals living with HIV, to peripartum ART for the prevention of transmission. This review aims to highlight the critical components that pediatric providers need to be aware of for optimal prevention and treatment of perinatal HIV infection.