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. It is recognized that DBA can be caused by mutations in 24 ribosomal protein (RP) genes, including RPS19, RPL5, and RPL11, as well as 6 non-ribosomal genes, such as GATA-1, EPO, and TP53. Despite the rarity of DBA, which results in a limited patient pool and a scarcity of research models, there is substantial uncertainty surrounding the pathogenic mechanisms associated with genetic mutations in DBA, and the clinical treatment options remain strikingly limited. This review synthesizes the findings from the zebrafish, mouse, and human cellular models of DBA mutations that researchers have developed in their pursuit to understand the disorder. It clarifies the pathogenic mechanisms and monitors the progression of drugs into clinical trials, thereby aiding in the further in-depth exploration of the etiology and therapeutic advancements for DBA.