The workup and management of neonatal thrombocytopenia is a problem commonly encountered by pediatric hematologists and neonatologists. The incidence of this problem has been estimated to range as high as 1% or more for healthy term infants to 20% of newborns admitted to a neonatal intensive care unit. An expeditious approach to this problem and timely intervention when necessary can prevent or attenuate the potentially serious consequences of this problem, most notably that of intracranial hemorrhage. In this article we discuss the incidence and causes of this problem, and present an algorithm for an approach to the neonate with thrombocytopenia. This will include consideration of fetal thrombocytopenia and its management, that is, in repeated pregnancies in women with alloimmune thrombocytopenia. Case discussions will be used to illustrate the algorithm.