To date, heart failure (HF) prognosis is still difficult: symptoms and signs are often non-specific, and poor sensitive indicators for HF severity. Brain natriuretic peptide (BNP) is now included in the current guidelines for HF diagnosis, management and risk assessment because of its high specificity and sensibility. BNP became a first-line exam in HF patients' evaluation at hospital admission together with clinical and chest X-ray. In discharged patients, the prognostic role of BNP is associated with decongestion and its significant reduction compared to admission level appears one of the best outcome predictors. In fact BNP measurement could identify patients with increased risk of adverse events and left ventricular remodeling. Although a single BNP value assay and the absolute value during hospitalization is related to the prognosis, especially at discharge. On the other hand, hormone levels could be influenced by several factors (i.e., renal dysfunction, anemia, age, liver insufficiency, Body Mass Index) independently from systemic and pulmonary congestion. Therefore, a new approach which considers a multimodality strategy including BNP assay among the traditional clinical examination and imaging studies should be routinely encouraged to better define cardiac dysfunction's etiology and severity, as well as to recognize patients at risk of adverse outcome.