Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML). Its exclusivity is reflected by both the clinical course and the management of patients. This article discusses 2 aspects of the unique management of patients with APL: the role of maintenance therapy and polymerase chain reaction (PCR) monitoring. Despite common practice, the efficacy of maintenance therapy in APL is still debated, and the introduction of arsenic trioxide into frontline protocols makes this debate even more challenging. This article also attempts to clarify details regarding the type and duration of maintenance treatment. The presence of residual leukemic cells, seen using PCR analysis of the PML/RARα fusion gene product, in patients who have experienced a complete response has been shown to have a high correlation with subsequent relapse. This fact led to the broad use of PCR monitoring techniques in patients with APL. Practicing clinicians face several questions with regard to monitoring, such as what is the best technique for monitoring patients with APL, who can benefit the most from these tests, what are the best time points, and for how long is monitoring recommended. These questions are addressed in this article.