Heart failure is a disease with high mortality and the risk of heart failure increases in magnitude with age. The patients of heart failure is increasing year by year. Hence, Pharmaceutical researchers have to develop new drugs with better pharmacological effects to coping with this phenomenon. In this article, we reviewed the small molecule compounds for heart failure that have been marketed in recent years or are promising to enter clinical research. We also reviewed the SAR (structure activity relationship) of these molecules, such as renin inhibitors, ROMK inhibitors, a kind of new diuretics, and some dual-targets inhibitors. These small molecules proven to be beneficial effect on heart failure patients. Which may provide ideas for the design of novel anti-heart failure therapeutic drugs.