The advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has revolutionized the treatment of acute promyelocytic leukemia (APL), resulting in excellent rates of remission and long-term survival. However, real-world outcomes often fall short of those observed in clinical trials due to various factors related to patient demographics and clinical practices. This review examines APL treatment outcomes in real-world settings and highlights the phenomenon of APL clusters. Clinical trials frequently exclude older patients and individuals with significant comorbidities, yet these groups represent a substantial portion of patients in clinical practice. Early mortality remains high in real-world settings, compounded by delayed diagnosis and treatment initiation, as well as the inexperience of some community providers and limited resources of their centers in managing APL and its associated complications. High rates of disease and induction-related complications further exacerbate