Alloimmune thrombocytopenia resulting from the destruction of platelets by an alloantibody elicited during the recipient’s immune response against platelets from a genetically different individual is not a rare event. Of alloimmune thrombocytopenias, the one with the greatest clinical significance is fetal and neonatal alloimmune thrombocytopenia (FNAIT), which affects 1:800 to 1:2000 live births in Caucasians. In case of severe thrombocytopenia, the most feared complication is intracranial hemorrhage leading to death or neurological impairment (10% and 20% of the reported cases in retrospective studies, respectively). Important developments have been made in diagnosis and therapy in recent years. However, there are still questions addressing the pathophysiology and the optimal management. Development of animal models and large collaborative studies are of importance for the better understanding of the implicated mechanisms, prevention, and specific therapies of this condition and its deleterious consequences.