Myeloperoxidase (MPO) is a glycoprotein released by activated polymorphonuclear neutrophils, which takes part in the defense of the organism through production of hypochlorous acid (HOCl), a potent oxidant. Since the discovery of MPO deficiency, initially regarded as rare and restricted to patients suffering from severe infections, MPO has attracted clinical attention. The development of new technologies allowing screening for this defect has permitted new advances in the comprehension of underlying mechanisms. Apart from its implications for host defense, the expression of MPO restricted to myeloid precursors makes MPO mRNA a good marker of acute myeloid leukemia. In addition, during the last few years, involvement of MPO has been described in numerous diseases such as atherosclerosis, lung cancer, Alzheimer's disease and multiple sclerosis. Both strong oxidative activity and MPO genetic polymorphism have been involved. This review summarizes the broad range of diseases involving MPO and points out the possible use of this protein as a new clinical marker and a future therapeutic target.