The longitudinal growth of long bones occurs in growth plates where chondrocytes synthesize cartilage that is subsequently ossified. Altered growth and subsequent deformity resulting from abnormal mechanical loading is often referred to as mechanical modulation of bone growth. This phenomenon has key implications in the progression of infant and juvenile musculoskeletal deformities, such as adolescent idiopathic scoliosis, hyperkyphosis, genu varus/valgus and tibia vara/valga, as well as neuromuscular diseases. Clinical management of these deformities is often directed at modifying the mechanical environment of affected bones. However, there is limited quantitative and physiological understanding of how bone growth is regulated in response to mechanical loading. This review of published work addresses the state of knowledge concerning key questions about mechanisms underlying biomechanical modulation of bone growth. The longitudinal growth of bones is apparently controlled by modifying the numbers of growth plate chondrocytes in the proliferative zone, their rate of proliferation, the amount of chondrocytic hypertrophy and the controlled synthesis and degradation of matrix throughout the growth plate. These variables may be modulated to produce a change in growth rate in the presence of sustained or cyclic mechanical load. Tissue and cellular deformations involved in the transduction of mechanical stimuli depend on the growth plate tissue material properties that are highly anisotropic, time-dependent, and that differ in different zones of the growth plate and with developmental stages. There is little information about the effects of time-varying changes in volume, water content, osmolarity of matrix, etc. on differentiation, maturation and metabolic activity of chondrocytes. Also, the effects of shear forces and torsion on the growth plate are incompletely characterized. Future work on growth plate mechanobiology should distinguish between changes in the regulation of bone growth resulting from different processes, such as direct stimulation of the cell nuclei, physico-chemical stimuli, mechanical degradation of matrix or cellular components and possible alterations of local blood supply.