Animal models are useful in research that examines physiological mechanisms and, as such, are invaluable in developing therapies to alleviate illness and promote health. Ethical considerations are essential for proper animal use and include replacement by nonanimal models where possible, reduction in the numbers of animals used, and refinement of experimental protocols to reduce animal suffering. Choosing the optimum model depends on the long- and short-term goals of the project, and the choice of a model goes hand in hand with appropriate study design. Five key features to think about when choosing a model are as follows: model asymmetry, necessary differences, specificity to the study, model validity, and model improvement. Appropriate use of both male and female animals has also become an important issue in recent times. These considerations will assist in understanding animal model use.