Heart failure has long been among the most fatal diseases worldwide. That calls for research and development of new approaches to heart failure. With two treatment principles: either to increase myocardial contraction in case of acute/advanced heart failure or to decrease workload for the heart in case of chronic heart failure, new drug candidates are expected to increase patient’s survival and quality of life. Medications are valuable if they are used to manage underlying risk factors or systemic/cardiovascular diseases as well. Among the newly investigated approaches, sodium-glucose cotransporter 2 inhibitors, angiotensin receptor/neprilysin inhibitor, and soluble guanylate cyclase stimulators/activators are the most successful ones. They have proved their superiority repeatedly in clinical trials of HFrEF treatment, and are all being investigated for HFpEF. Targeting cardiac myofilaments, myosin modulators aims to change the heart contractility without affecting intracellular calcium level. Besides that, cardiac metabolism pathway and the hallmark of metabolism shifting in heart failure open up a new promising direction. Inflammatory background also plays an important role in pathogenesis, so various anti-inflammatory approaches have been tried for management of heart failure.