Biomechanical factors play an important role in the health of diarthrodial joints. Altered joint loading – associated to obesity, malalignment, trauma or joint instability – is a critical risk factor for joint degeneration, whereas exercise and weight loss have generally been shown to promote beneficial effects for osteoarthritic joints. The mechanisms by which mechanical stress alters the physiology or pathophysiology of articular cartilage or other joint tissues likely involve complex interactions with genetic and molecular influences, particularly local or systemic inflammation secondary to injury or obesity. Chondrocytes perceive physical signals from their environment using a variety of mechanisms, including ion channels, integrin-mediated connections to the extracellular matrix that involve membrane, cytoskeletal and intracellular deformation. An improved understanding of the biophysical and molecular pathways involved in chondrocyte mechanotransduction can provide insight into the development of novel therapeutic approaches for osteoarthritis.