Premature infants admitted to the neonatal intensive care unit are at risk for severe infections and infectious complications caused by vaccine-preventable diseases. Both maternal and neonatal vaccination prevent such infections and improve outcomes for premature infants. An understanding of vaccine efficacy, safety, and administration recommendations, as well as reasons for vaccine hesitancy among clinicians and caregivers, facilitate strategies for improving vaccination rates for infants in the neonatal intensive care unit. Timely vaccination of premature infants confers important protection and improves vaccination rates during childhood.