Inherited thrombocytopenias (ITs) consist of a highly heterogeneous group of at least 48 disorders caused by alterations of at least 45 genes and characterized by varying degrees of complexity of the clinical picture and extreme variability in prognosis. In some forms, thrombocytopenia, with or without platelet dysfunction, is the only clinical manifestation. In other forms, the platelet defect is associated with further congenital phenotypes. Finally, some relatively frequent ITs are insidious conditions characterized by the propensity to acquire additional diseases, such as hematological malignancies, bone marrow aplasia, or extra-hematological manifestations, which often affect the prognosis much more than thrombocytopenia itself. The investigation of the pathogenesis of ITs allows highlighting the essential roles of numerous mechanisms that regulate platelet biogenesis and/or survival. The introduction of high-throughput sequencing in diagnostics has revolutionized the diagnostic approach to ITs. However, the interpretation of data provided by massive sequencing techniques is often challenging and requires close collaboration of physicians, geneticists, non-clinical platelet experts, and bioinformaticians with expertise in the field of these rare conditions. Finally, recent advances in the molecular and clinical characterization of ITs have led to significant improvements in the clinical management and treatment of affected individuals.