In the past three decades, finite element (FE) modelling has provided considerable understanding to the area of musculoskeletal biomechanics. However, most of this understanding has been generated using generic, standardised or idealised models. Patient-specific modelling (PSM) is almost never used for making clinical decisions. Imaging technologies have made it possible to create patient-specific geometries and FE meshes for modelling. While these have brought us closer to PSM, several challenges associated with the definition of material properties, loads, boundary conditions and interaction between components still need to be overcome. This study reviews the current status of PSM with respect to defining material behaviour and prescribing boundary conditions and interactions. With regard to the constitutive modelling of bone, it is seen that imaging is being increasingly used to define elastic properties (isotropic as well as anisotropic). However, the post-elastic and time-dependent behaviour, important for several modelling situations, is mostly obtained from in vitro experiments. Strain-based plasticity, not commonly available in FE codes, appears to have the potential of reducing an element of patient-specificity in modelling the yielding behaviour of bone. PSM of real boundary conditions that include muscles and ligaments continues to remain a challenge; many clinically relevant questions can be, however, answered without their inclusion. Simulation techniques to undertake PSM of interactions between bone and uncemented implants are available. Interference fit employed in both joint replacement fracture treatments induces considerable preload whose inclusion in models is important for the prediction of interface behaviour. Copyright © 2012 John Wiley & Sons, Ltd.