The benefits of cardiac rehabilitation (CR) have been demonstrated in patients after myocardial infarction (MI), and in patients with chronic heart failure (HF). The core components of the CR program include improvement in exercise tolerance and optimization of coronary risk factors (i.e., lipid and lipoprotein profiles, body weight, blood glucose levels, blood pressure levels, and smoking cessation). Indeed, CR has been shown to improve exercise capacity, control of cardiovascular risk factors, quality of life, hospital readmission, and mortality rates. Nonetheless, pre- and clinical CR and exercise training models are an enormous source of potential beneficial mechanisms that can be exploited for cardiac disease therapy. Consequently, in this review, we aim to explore the unique benefits of CR in HF and coronary artery disease, focusing on the epigenetic mechanisms involved and their translational relevance. These mechanisms may represent novel therapeutic targets to promote functional recovery after cardiac injury, and non-coding RNAs could be predictive biomarkers for CR success in patients.