The infection rate and the infection related fatality rate of Streptococcus pneumoniae in children are high globally, especially in preterm infants. Because of the low immunity in preterm infants, the effectiveness of vaccination against Streptococcus pneumoniae is uncertain, and thus the vaccination is often delayed. Furthermore the risk of vaccine related adverse reactions such as apnea and bradycardia in preterm infants is high. The immunological effect, timing and safety of Streptococcus pneumoniae vaccine in premature infants were reviewed.