Reactive oxygen species (ROS) play a dual role in the pathophysiology of acute myeloid leukemia (AML), functioning as both signaling molecules and agents of cellular damage. This review offers an in-depth analysis of ROS production in AML, highlighting their impact on essential cellular pathways that govern cell survival, proliferation, and apoptosis. It explores both natural and synthetic pharmacological agents that modulate ROS generation and enhance oxidative stress, assessing their therapeutic potential and the challenges they present in clinical practice. Additionally, the review identifies ROS-associated prognostic biomarkers that could enhance patient stratification and improve treatment outcomes in AML. Despite the promising potential of ROS-targeted therapies, significant challenges remain, such as the complexity of ROS dynamics, resistance mechanisms, and the influence of the tumor microenvironment. This review aims to shed light on current advancements and emphasize the need for further research to refine therapeutic strategies that leverage the ROS pathway in AML.