Scientists have long utilized model organisms to answer fundamental questions about biology. Zebrafish, rodents, swine, and primates represent just a few of the many models commonly leveraged for biomedical research. They are especially important in translational research and advancing our knowledge of human disease. For surgeon-scientists, modeling the conditions that affect our patients is essential to elucidating the underlying pathophysiology and to discovering novel therapies. Familiarity with the various model organisms available and their respective strengths is therefore essential so that the best system is selected to answer a scientific question. Here we present a selection of model organisms and the uses, drawbacks, and practical aspects thereof to provide a brief review for the surgeon-scientist.