Oxidative stress (OS) has been characterized by an imbalance between the production of reactive oxygen species (ROS) and a biological system's ability to repair oxidative damage or to neutralize the reactive intermediates including peroxides and free radicals. High ROS production has been associated with significant decrease in antioxidant defense mechanisms leading to protein, lipid and DNA damage and subsequent disruption of cellular functions. In humans, OS has been reported to play a role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Lou Gehrig's disease, multiple sclerosis and Parkinson's disease, as well as atherosclerosis, autism, cancer, heart failure, and myocardial infarction. Although OS has been linked to the etiology and development of chronic diseases, many chemotherapeutic drugs have been shown to exert their biologic activity through induction of OS in affected cells. This review highlights the controversial role of OS in the development and progression of leukemia cancer and the therapeutic application of increased OS and antioxidant approaches to the treatment of leukemia patients.