By 1892, Julius Wolff and others realized that mechanical loads can affect bone architecture in living beings, but the mechanisms responsible for this effect were unknown, and it had no known clinical applications. In 2003 we know how this effect occurs and some of its applications. Our load-bearing bones (LBBs) include tibias, femurs, humeri, vertebrae, radii, mandibles, maxillae, wrists, hips, etc (so LBBs are not limited to weight-bearing ones). The strength of such bones and their trabeculae would represent their most important physiologic feature but in the special sense of relative to the size of the typical peak voluntary loads on them. The biologic "machinery" that determines whole-bone strength forms a tissue-level negative feedback system called the mechanostat. Two thresholds make a bone's strains determine its strength by switching on and off the biologic mechanisms that increase or decrease its strength. Equally, two thermostats can determine a room's temperature by switching on and off the room's heating and cooling systems. General features show that the largest voluntary loads on LBBs determine most of their strength after birth. These loads come from muscle forces so muscle strength strongly influences the strength of our LBBs. This process affects, in part, the healing of fractures, bone grafts, osteotomies, and arthrodeses; the bone's ability to endure load-bearing joint and dental endoprostheses; why healthy bones are stronger than the minimum needed to keep voluntary loads from breaking them suddenly or from fatigue; some general functions and disorders of bone modeling and basic multicellular unit-based bone remodeling; some limitations of in vitro data and of pharmaceutical actions; and the fact that many bone-active humoral and local agents have permissive roles in a bone's adaptations and healing, instead of forcing them to occur.