Infection is one of the most common complications associated with medical interventions and implants. As tissue engineering strategies to replace missing or damaged tissue advance, the focus on prevention and treatment of concomitant infection has also begun to emerge as an important area of research. Because the in vivo environment is a complex interaction between host tissue, implanted materials, and native immune system that cannot be replicated in vitro, animal models of infection are integral in evaluating the safety and efficacy of experimental treatments for infection. In this review, considerations for selecting an animal model, established models of infection, and areas that require further model development are discussed with regard to cutaneous, fascial, and orthopedic infections.