This chapter reviews general concepts of spinal instability and stabilization. It focuses on animal models that have been used to evaluate novel osteoinductive growth factors or implantable, fusion enhancing biomaterials. The chapter discusses the models that enable examination of systemic factors influencing the fusion process. A simulation of lumbar instability, examining passive and active stabilization components, was developed in an in vivo porcine model. In vivo animal models of destabilization and fixation are necessary to examine the effects of skeletal repair and intersegmental fusion on intersegmental instability. The canine, sheep, and porcine models have been most commonly used to examine both anterior and posterior instability and fixation in the thoracic and lumbar spines in vivo. Canines have historically been the most commonly used animal models to examine factors that influence the spinal fusion process. The posterior intertransverse process fusion is the most relevant and useful of the posterior fusion techniques for extrapolating data to the human condition.