The mechanism(s) by which chondrocytes convert physical stimuli to intracellular signals, which in turn direct cell activities, represents an area of intense current orthopaedic tissue engineering research. This report is aimed at providing an overview of some biomechanical engineering factors that are required for pursuing this type of research. Two specific aspects of cartilage are addressed:​ (1) how does the tissue function biomechanically;​ and (2) what is the nature of physical stimuli inside articular cartilage. By focusing on the effects of inhomogeneities of material properties, a description of some of the mechanical and electrochemical events (the physical stimuli) that would occur in cartilage during loading is presented. Two simple and common tests are considered:​ permeation and confined compression. Theoretical analyses using appropriate constitutive laws (the biphasic and triphasic theories) reveal the details of how surface loadings are converted to mechanical and electrochemical signals by the extracellular matrix to hydraulic and osmotic pressures, fluid, solute and ion flows, matrix deformations, and electrical fields. The material inhomogeneities are shown to be able to significantly change the mechanical and electrochemical events within the extracellular matrix, and thus the environments around chondrocytes. Material inhomogeneities arising from the flow of interstitial fluid through the porous and permeable extracellular matrix also are discussed. In the authors’ view, the charged extracellular matrix, together with the associated interstitial fluid and ions, collectively can be thought of as a signal transducer. Knowledge of the nature of the mechanical and electrochemical events in the extracellular matrix, and their variations with time and location during and after loading, is essential in the understanding of the mechanical signal transduction mechanism(s) in chondrocytes and articular cartilage.