The ultimate goal of heart failure (HF) treatment is to improve the prognosis of patients. Previous basic, clinical, and population studies have advanced the modern treatment of HF, but efficacy is still limited especially in 'real world' patients. There are 2 approaches to solve this crucial issue. First is the further development of novel therapeutic strategies based on new insight into the pathophysiology of myocardial remodeling and failure. Second is the improvement of the quality of care in routine clinical practice. The basic approach is to develop the treatment of myocardial remodeling by regulating mitochondrial oxidative stress. In the failing heart, oxygen radicals are the result of defects of mitochondrial electron transport, causing mitochondrial DNA damage and functional decline, and further production of oxygen radicals. Oxidative stress causes myocyte hypertrophy, apoptosis, and interstitial fibrosis by activating matrix metalloproteinases, all of which result in myocardial remodeling and failure. Therefore, mitochondrial oxidative stress and DNA damage are good therapeutic targets. The clinical approach is to develop effective strategies of HF management for the 'real world' patients. Readmission because of exacerbation is common in HF patients and further impairs their quality of life. Noncompliance with treatment is the most common precipitating factor for readmission. Regular medical follow-up and social support are important components that should be included in the disease management program of HF patients. These basic and clinical approaches are needed to establish new and effective treatment strategies for Japanese patients with HF.