Nearly 10% of premature and critically ill infants receive fresh-frozen plasma (FFP) transfusions to reduce their high risk of bleeding. The authors have only limited data to identify relevant clinical predictors of bleeding and to evaluate the efficacy of FFP administration. There is still no consensus on the optimal use of FFP in infants who have abnormal coagulation parameters but are not having active bleeding. The aims of this review are to present current evidence derived from clinical studies focused on the use of FFP in neonatology and then use these data to propose best practice recommendations for the safety of neonates receiving FFP.