Different species vary in bone metabolism, especially in modeling and remodeling of the bone. Human-related diseases with severe outcomes on bone, such as osteoporosis or osteoarthritis, are often reflected in animal models, which cannot adequately mimic the human situation. The pre-clinical investigation of implant materials in vivo complicates the search for the ideal animal model, especially when combining pathologic bone diseases and implant material. For instance, while alterations in trabecular bone architecture are investigated in female osteoporotic rats, rodents commonly lack cortical bone remodeling or secondary osteon formation. Small ruminants are commonly used to study long bone defects or orthopedic materials, due to their comparability to humans regarding body weight, bone size, and fracture healing. Nevertheless, there are important differences between human and ruminant models: plexiform cortical bone, seasonal bone loss, and stronger trabecular bone appear in sheep compared to humans. This chapter will summarize fundamental differences in bone quality between different animal models used for orthopedic and implant material research. Thus, choosing the ideal animal model to answer the proposed research question remains the key to guarantee a solid and excellent scientific study.