Neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe thrombocytopenia in the healthy newborn, occurring in 1 in 1000 live births. NAIT is analogous to rhesus alloimmunization in pathophysiology; however, it often presents unexpectedly in first pregnancies. Presentation of NAIT varies from mild thrombocytopenia to life-threatening intracranial hemorrhage. It has been observed to be more severe in subsequent affected pregnancies. It is important that the diagnosis of NAIT be considered in the work-up of all cases of neonatal thrombocytopenia to determine the risk to future pregnancies and corresponding management plans. This article discusses the pathogenesis and incidence of NAIT and the antenatal and postnatal management of this condition.