Abstract: Heart failure (HF), a serious and end stage of numerous types of cardiovascular diseases, has brought a heavy burden to the public related to its high morbidity, mortality, and hospitalization rate. Excessive activation of neuroendocrine, especially the renin-angiotensin-aldosterone system (RAAS), is pivotal in the pathological process of HF. RAAS inhibitors (ACEIs/ARBs, aldosterone receptor antagonists) have been the cornerstone in HF treatment. In recent years, remarkable advances in HF treatment have been made. Sacubitril/valsartan (LCZ696) presents superiority to enalapril in PARDIGM-HF and this is a significant breakthrough in HF therapy over the past two decades. Our research, published in ESC Heart Fail, has demonstrated that supramaximal-dose of ACEIs/ARBs is superior to normal-dose in HF treatment. Many new therapeutic targets have emerged as novel strategies for HF treatment as the exploration into RAAS continues into the future and key findings are elaborated on in this review.