Mechanotransduction is the process by which physical forces are converted into biochemical signals that are then integrated into cellular responses. It plays a crucial role in bone repair and regeneration and thus has attracted a great deal of interest from researchers in various fields. This report reviews the current clinical evidence that shows the role mechanotransduction plays in bone processes such as physical adaptation, pathological fracture healing, and therapeutic distraction osteogenesis. We also outline the progress that has been made in understanding bone mechanotransduction from both the macro- and microperspectives. Specifically, we describe the theories that postulate how mechanical force exhibits effects on bone repair and regeneration (i.e., the tensegrity and mechanosome theories). We also summarize the recent advances in our understanding of the molecular signaling pathways of mechanotransduction, which include calcium ion channels, integrins, Wnt/β-catenin, prostaglandin, and nitric oxide. A better understanding of skeletal mechanotransduction will facilitate research into this promising field and could lead to the development of applications that improve bone structures and functions.