The measurement of circulating brain natriuretic peptide (BNP) and its related peptide, the N-terminal fragment of proBNP (NT-proBNP), have a high degree of diagnostic accuracy and clinical relevance both in acute and chronic heart failure (HF). However, the role of measurement of BNP/NT-proBNP in the follow-up of treated HF patients is still debated. In this chapter, authors have studied the clinical impact of B-type natriuretic peptide assay in the follow-up of patients with heart failure, and, in particular, the possible role of the measurement of its circulating levels in guiding the treatment. A relatively small number of randomized studies were designed to specifically evaluate the clinical use of BNP/NT-proBNP assay in monitoring and tailoring the medical therapy in HF patients. A meta-analysis of results reported in these studies indicate that the inefficacy to improve the mortality rate of the peptide-guided compared to the control group found in some studies, may depend on to the inability of current therapeutic strategies to modify prognosis, especially in the elderly subset of patients, who are characterized by more advanced disease and comorbidities. Further prospective and randomized clinical studies are necessary to definitively demonstrate whether BNP/ NT-proBNP-guided therapy is able to significantly improve the outcome of patients with HF.