Certain exercises can induce osteogenesis and improve bone strength, yet the biological processes involved in bone mechanotransduction are only beginning to be understood. Several pathways are emerging from current research, including calcium signaling associated with membrane ion channels, adenosine triphosphate signaling, second messengers such as prostaglandins and nitric oxide, and signaling involving mitogen-activated protein kinase. One characteristic of the mechanosensing apparatus that has only recently been studied is the important role of desensitization. Experimental protocols that insert "rest" periods to reduce the effects of desensitization can double anabolic responses to mechanical loading. Exercises that reduce desensitization may provide an effective means to build bone strength.