In recent years natriuretic peptides (NPs) have emerged as important tools for evaluation of heart failure patients. Since its approval by the Food and Drug Administration (FDA) in November 2000, recent surveys suggest that approximately 83% of hospitals in the US use some type of NP testing. Although NP testing was originally focused on rapid diagnosis of patients presenting to the emergency department with shortness of breath, clinicians regularly look to NPs for diagnosing minimally symptomatic or asymptomatic left ventricular dysfunction, and using NPs levels in clinic to help ascertain when decompensation is present. NP testing is now included in the guidelines for the diagnosis and treatment of chronic heart failure and in the Italian Consensus Document for the clinical use of NPs. Recommendations indicate that assessment of NPs can be considered a reliable rule-out test of heart failure in primary care and in the emergency room even if they stated that the role for treatment monitoring or for prognostic evaluation needs to be determined. In recent years, cardiac resynchronization therapy (CRT) was introduced as a new treatment modality for patients with systolic heart failure and several studies suggest that plasma concentration of NPs ensues as a very useful parameter for evaluating and monitoring patients who undergo CRT. Thus this article aims not only to summarise data concerning NPs measurement in patients with heart failure, but also to indicate how these markers could be utilized in the future to objectively assess effects of CRT (identification of responders). In conclusion, if further studies will confirm above mentioned remarks, it would be possible that NPs evaluation can help to tailor the more suitable therapy for each heart failure patient and, therefore, to reduce the number of failures.