Acute heart failure (AHF) is a life-threatening condition with a dramatic burden in terms of symptoms, morbidity and mortality. It is a specific syndrome requiring urgent, life-saving treatment. Multiple specific pathophysiologic mechanisms may be involved, including congestion, inflammation, and neurohormonal activation. This process eventually leads to symptoms, end-organ damage, and adverse outcomes. Clinical presentation varies, but it almost universally includes worsening of congestion associated with different degrees of hypoperfusion. Due to substantial early symptoms burden and high morbidity and mortality, patients with AHF require intensive monitoring and intravenous treatment. However, beyond variable improvement in congestion, none of the available intravenous therapies for AHF was shown to improve longer term outcomes. Although oral treatment with guideline-directed therapies for stable patients with HF and reduced ejection fraction (HFrEF) before discharge may fully prevent subsequent episodes, proof that this strategy may benefit patients is lacking. First, most patients with AHF have preserved EF (HFpEF) where no therapies have been shown to be effective. Second, all therapies developed for patients with HFrEF were tested for efficacy on outcomes in patients who were stable without recent AHF. Hence, the implementation of these chronic therapies during an AHF episode is untested. Third, the problem to better treat AHF patients in their early phase remains crucial with treatment strategies largely untested, yet. Further studies targeting AHF specific mechanisms, such as inflammation and end-organ damage, and finding effective intravenous drugs remain therefore warranted.