This chapter outlines key considerations and methodologies for conducting in vivo studies using animal models to assess the safety and efficacy of tissue-engineered neocartilage. It begins with a discussion of cell source selection, including the development of analogous cellular products and the establishment of preclinical cell banks. The advantages and disadvantages of widely used animal models are discussed, including both small and large animal models. Next, the chapter describes methods used to evaluate implant safety and efficacy in vivo, such as arthroscopy, blood panels, imaging modalities, pain scales, gait analysis, activity monitoring, and the adaptation of clinical histological scoring systems for preclinical research. Overall, these sections provide a framework for designing and carrying out preclinical studies in cartilage repair.