Acute myocardial infarction (AMI), and the heart failure (HF) that often follows, are leading causes of death and disability worldwide. Crucially, there are currently no effective treatments, other than myocardial reperfusion, for reducing myocardial infarct (MI) size and preventing HF following AMI. Thus, there is an unmet need to discover novel cardioprotective therapies to reduce MI size, and prevent HF in AMI patients. Although a large number of therapies have been shown to reduce MI size in experimental studies, the majority have failed to benefit AMI patients. Failure to deliver cardioprotective therapy to the ischemic heart in sufficient concentrations following AMI is a major factor for the lack of success observed in previous clinical cardioprotection studies. Therefore, new strategies are needed to improve the delivery of cardioprotective therapies to the ischemic heart following AMI. In this regard, nanoparticles have emerged as drug delivery systems for improving the bioavailability, delivery, and release of cardioprotective therapies, and should result in improved efficacy in terms of reducing MI size and preventing HF. In this article, we provide a review of currently available nanoparticles, some of which have been FDA-approved, in terms of their use as drug delivery systems in cardiovascular disease and cardioprotection.