Goals of treatment in acute heart failure (AHF) are different with regard to the clinical presentation, etiology and hemodynamic profiles. Therefore AHF is a colorful picture that encompasses several syndromes with particular characteristics. Unfortunately the protocol treatments proposed until now regarding old and new drugs, showed neutral or negative results in most of trials. This could depend on patient population selection, syndrome heterogeneity, drugs used, administration and posology, study design and study target. Most of the trials showed positive results in the early period but any improvement in mortality and re-hospitalization at a later stage. In this review we summarize the drugs more commonly used in AHF syndromes on the basis of pressure values, organ perfusion, pulmonary and venous congestion. However, a significant improvement in outcome needs to consider not only the acute phase but the effect of each drug on cardiac damage, organ perfusion, neurohormonal activation and renal injury after a short period. The most important goal of treatment should be an outcome improvement at the post-discharge phase. This could be obtained in the future assuming an 'holistic' point of view looking for all the potential consequences and benefits at both cardiac and systemic levels.