Perioperative cardioprotection aims to minimize the consequences of myocardial ischemia-reperfusion injury. In isolated tissue and animal experiments, several treatments have been identified providing cardioprotection. Some of these strategies have been confirmed in clinical proof-of-concept studies. However, the final translation of cardioprotective strategies to really improve clinical outcome has been disappointing: large randomized controlled clinical trials mostly revealed inconclusive, neutral, or negative results. This review provides an overview of the currently available evidence regarding clinical implications of perioperative cardioprotective therapies from an anesthesiological perspective, highlighting nonpharmacological as well as pharmacological strategies. We discuss reasons why translation of promising experimental results into clinical practice and outcome improvement is hampered by potential confounders and suggest future perspectives to overcome these limitations.