Seymour J. Klebanoff, MD, PhD (1927–2016) was a major contributor to the discovery and understanding of the NADPH oxidase (Nox) family of enzymes, particularly in the context of peroxidase-catalyzed halide oxidation by the Nox product hydrogen peroxide (H2O2). His pioneering work beginning in the 1960s proved that myeloperoxidase (MPO) is a key component of the neutrophil microbicidal armamentarium. He devoted much of his career to exploring the many biochemical and biological roles of the MPO-H2O2-halide system in innate immunity, antimicrobial host defenses, and the pathophysiology of disease. Klebanoff was also a much-admired mentor and role model for numerous young investigators, most notably physician scientists, many of whom went on to highly productive careers and leadership positions in academic medicine. He received many honors, including election to the US National Academy of Sciences and US Institute of Medicine, as well as receipt of the Alexander Fleming Award, Bristol-Meyers Squibb Award, and Lifetime Achievement Award of the Association of American Medical Colleges.