The first question to ask when deciding which model to use for the preclinical testing of a therapeutic agent should be: What exactly is it that the chosen model is attempting to model? Therefore, in the context of intra-abdominal models of infection, the question becomes, is the goal to mimic diffuse peritonitis, intra-abdominal abscesses, septic shock, or a multiple organ dysfunction-type syndrome. Having decided on the clinical situation to model, it becomes important to ensure that the model is as congruent with the clinical situation as feasible, especially when the goal is the preclinical testing of possible therapeutic agents. Consequently, different types of rodent intra-abdominal infection models will be reviewed, focusing on their rationales as well as their strengths and weaknesses as models of clinical disease.