Myoglobin is a cytoplasmic hemoprotein that is restricted to cardiomyocytes and oxidative skeletal muscle fibers. Myoglobin is a well-characterized protein and numerous studies have established that it has an essential role in facilitated oxygen transport in striated muscles. Recent strategies, using gene disruption technologies, have produced mice that lack myoglobin. These myoglobin deficient mice have a binary phenotype and a subpopulation of these mutant mice is viable and fertile. Characterization of the viable myoglobin null mice has uncovered a number of molecular and cellular adaptive mechanisms that function to promote oxygen delivery in the mutant striated muscle cell. Moreover, cellular and physiological studies, using the myoglobin deficient mouse model, support the conclusion that the functions of myoglobin include: facilitated oxygen transport, the storage of oxygen and a scavenger of nitric oxide or reactive oxygen species. Collectively, the use of genetic mouse models will further enhance our understanding of myoglobin function in normal and pathological muscle lineages.