Vaccine-preventable diseases may be serious and even life threatening in premature infants. Opportunities for immunization are frequently missed due to parental or healthcare personnel misconceptions on safety or immunogenicity of vaccines in these children. In addition, the impact of infectious diseases is frequently underestimated in preterms. There is no evidence of a higher incidence rate of vaccine associated adverse reactions in premature babies. For the majority of preterm infants vaccines provide protection against severe disease except for those extremely premature (less than 1500 grs) in whom the immune response may be less. Adherence to the EPI Vaccine Program is critical in this population with an immunization schedule similar to that of term infants, following chronological age. Premature follow-up programs should include additional vaccines not included in the EPI Program, such as conjugated pneumococcal vaccines and annual influenza inactivated vaccine. An additional strategy to protect preterms is the strict adherence to vaccination schedule among contacts including use of special vaccines in older children and adult contacts such as influenza and acellular pertussis vaccines.