With the astounding morbidity and mortality associated with heart failure (HF), preventive approaches have been explored. Controlling hypertension to prevent HF is well-established, especially with sodium restriction and thiazide-based antihypertensive therapies showing potential advantages. Control of dyslipidemia with aggressive statin therapy is particularly beneficial in preventing HF in the setting of acute coronary syndrome. The HOPE study also established the benefit of ACE inhibitors in the prevention of HF in high-risk subjects. Meanwhile old data supporting tight glycemic control in preventing HF have not been confirmed, suggesting the complexity of diabetic cardiomyopathy. Avoiding tobacco use and other known cardiotoxins are likely helpful. While there has been substantial development in identifying biomarkers predicting future development of HF, therapeutic interdiction guided by biomarker levels have yet to be established, even though it offers hope in modulating the natural history of the development of HF in at-risk individuals.