Diamond-Blackfan anemia (DBA), also known as congenital pure red cell aplasia, is a rare genetic disorder characterized by bone marrow failure, congenital anomalies, and severe red blood cell abnormalities. The rarity of the condition, and consequently limited patient pool and scarcity of research models, means that the pathogenic mechanisms associated with genetic mutations in DBA remain uncertain, and the clinical treatment options are limited. This review synthesizes the findings from zebrafish, mouse, and human cellular models of DBA mutations. We clarify the pathogenic mechanisms and monitor the progression of drugs into clinical trials, thereby aiding further in-depth explorations into the etiology and therapeutic advancements for DBA.