Thrombocytopenia is a very common hematological abnormality found in newborns, especially in preterm neonates. Two subgroups can be distinguished: early thrombocytopenia, occurring within the first 72 hours of life, and late thrombocytopenia, occurring after the first 72 hours of life. Early thrombocytopenia is associated with intrauterine growth restriction, whereas late thrombocytopenia is caused mainly by sepsis and necrotizing enterocolitis (NEC). Platelet transfusions are the hallmark of the treatment of neonatal thrombocytopenia. Most of these transfusions are prophylactic, which means they are given in the absence of bleeding. However, the efficacy of these transfusions in preventing bleeding has never been proven. In addition, risks of platelet transfusion seem to be more pronounced in preterm neonates. Because of lack of data, platelet transfusion guidelines differ widely between countries. This review summarizes the current understanding of etiology and management of neonatal thrombocytopenia.