Bone is a living composite material that has the capacity to adapt and respond to both internal and external stimuli. This capacity allows bone to adapt its structure to habitual loads and repair microdamage. Although human bone evolved to adapt to normal physiologic loading (for example from gravitational and muscle forces), these same biological pathways can potentially be activated through other types of external stimuli such as pulsed electromagnetic fields, mechanical vibration, and others. This review summarizes what is currently known about how human bone adapts to various types of external stimuli. We highlight how studies on sports-specific athletes and other exercise interventions have clarified the role of mechanical loading on bone structure. We also discuss clinical scenarios, such as spinal cord injury, where mechanical loading is drastically reduced, leading to rapid bone loss and permanent alterations to bone structure. Finally, we highlight areas of emerging research and unmet clinical need.