In silico, defined in analogy to in vitro and in vivo as those studies that are performed on a computer, is an essential step in problem-solving and product development in classical engineering fields. The use of in silico models is now slowly easing its way into medicine. In silico models are already used in orthopaedics for the planning of complicated surgeries, personalised implant design and the analysis of gait measurements. However, these in silico models often lack the simulation of the response of the biological system over time. In silico models focusing on the response of the biological systems are in full development. This review starts with an introduction into in silico models of orthopaedic processes. Special attention is paid to the classification of models according to their spatiotemporal scale (gene/protein to population) and the information they were built on (data vs hypotheses). Subsequently, the review focuses on the in silico models used in regenerative orthopaedics research. Contributions of in silico models to an enhanced understanding and optimisation of four key elements-cells, carriers, culture and clinics-are illustrated. Finally, a number of challenges are identified, related to the computational aspects but also to the integration of in silico tools into clinical practice.