This review summarizes our current understanding of the influence of myostatin on bone cell metabolism and differentiation (direct regulator) and whole bone phenotypes (indirect regulator; via mechanosensation) of animal models partially or completely devoid of myostatin and highlights investigations of the skeletal impact of genetic and pharmacological inhibition of myostatin in osteogenesis imperfecta (OI), osteoporosis, osteoarthritis, Duchenne muscular dystrophy (DMD) and diabetes; pulling together data from human, murine, and canine studies. The gene discussed is MSTN; the disease is osteogenesis imperfecta.