Bone is a remarkable tissue that can respond to external stimuli. The importance of mechanical forces on the mass and structural development of bone has long been accepted. This adaptation behaviour is very complex and involves multidisciplinary concepts, and significant progress has recently been made in understanding this process. In this review, we describe the state of the art studies in this area and highlight current insights while simultaneously clarifying some basic yet essential topics related to the origin of mechanical stimulus in bone, the biomechanisms associated with mechanotransduction, the nature of physiological bone stimuli and the test systems most commonly used to study the mechanical stimulation of bone.