Over the past two decades there has been a concerted effort to identify interventions that can reduce the injury to the heart that occurs with an ischemic insult. Investigations in this field have relied heavily on animal models. Because these studies have been performed in a variety of animal models and have often produced conflicting conclusions, the reader must appreciate the strengths and limitations of each model in order to decide where the truth actually lies. This paper reviews the various animal models currently in use. We evaluate the strengths and weaknesses of each, explore the choice of endpoints, point out complications associated with each, and indicate how the results from each model can be interpreted.