The skeleton has provided many advantages during the course of vertebrate evolution, but it has also contained limitations that have strongly influenced bone biology. These limitations have included weight and the potential for fatigue failure. Calcified bone tissue is approximately twice as heavy as other tissues, so it is important to minimize the size of the skeleton, but this implies increasing bone stresses and strains and the potential for fatigue fracture. This paper first explores the role of fatigue damage removal by remodeling in extending a long bone's fatigue life to match the animal's lifetime. Next, an estimate is obtained for the amount that the cross-sectional area of a bone would have to be increased in lieu of remodeling to achieve the same extension of fatigue life, provided that the associated muscle mass remained constant. The result illustrates how remodeling can provide a gracile bone the same fatigue life as a substantially more robust bone lacking remodeling. Finally, it is shown that if muscle mass increases in linear proportion to bone mass, as experimental data suggest, extending a bone's fatigue life by increasing its cross-sectional dimensions may not be effective because the inertia of bigger bones would result in larger muscles and increased skeletal loads. Thus, bone remodeling to remove fatigue damage may be essential for the existence of relatively large, long-lived vertebrates.