In the past year, there has been increasing attention towards understanding the clinical relevance of minimal residual disease (MRD) assessment. The monitoring of MRD levels at various stages of therapy has considerable potential to impact the guidance of treatment for AML patients and improve outcomes. Thus, efforts have increased to address important concerns regarding MRD measurements. These concerns include: (1) what should be monitored; (2) what methodologies should be used; (3) whether such methodologies are standardized across laboratories; (4) how prognostic levels are defined; (5) when MRD should be monitored; and (6) what treatment options are available for MRD positive patients. In this review, we will discuss the methodologies available for MRD and the studies available to date aiming to address the concerns around the use of MRD measurements for AML patients.