In vivo animal models are currently the gold standard for testing the capacity of stem/progenitor cells, smart biomaterials and novel growth factors for successful tissue engineering. In vitro models ultimately fail to provide the appropriate physiologically relevant microenvironment and hence animal models are an essential pre-requisite in the translation of any new therapy to the clinic. The aim of this chapter is to consider the available animal models commonly in use for tissue engineering, with a particular focus upon bone and cartilage research. Factors driving the choice of a given animal model are reviewed, according to the requirements of experimental design, hypothesis and the specific parameters to be tested. A number of animal models, together with their respective advantages and limitations are described, ranging from relatively simple experimental designs such as the subcutaneous implant and muscle pouch models, through to the diffusion chamber model and chorioallantoic membrane assay, to the more complex in vivo bioreactors and (arguably the most clinically relevant) bone and cartilage defect models. The need to consider the ethical issues of using animal models and the principles of reduction, replacement and refinement are emphasised in selecting the final experimental model of choice.