The article presents advanced computer simulations aimed at the accurate modelling of human tibio-femoral joints (TFJs) in terms of anatomy, physiological loading and constitutive behaviour of the tissues. The main objective of this research is to demonstrate the implications that the implementation of different articular cartilage models have on the prediction of the joint response. Several biphasic material constitutive laws are tested using a finite element package and compared to the monophasic linear elastic description, often still used to predict the instantaneous response of the cartilage in 3D knee models. Thus, the importance of adequately capturing the contribution of the interstitial fluid support is proved using a simplified 3D model; subsequently, a biphasic poroviscoelastic non-linear constitutive law is implemented to study the response of a patient-specific TFJ subjected to simplified walking cycles. The time evolution of stresses, pore pressure, contact areas and joint displacements is captured and compared with existing meniscectomised knee models. Contact pressures and areas obtained using the developed numerical simulations are in agreement with the existing experimental evidence for meniscectomised human knee joints. The results are then used to predict the most likely site for the origin of mechanical damage, i.e. the medial cartilage surface for the specific case analysed in the present contribution. Finally, future research directions are suggested. © 2013 © 2013 Taylor & Francis.