Natriuretic peptides (NP) are secreted by cardiomyocytes and are reliable markers of cardiac dysfunction and cardiovascular risk by reflecting myocardial stress due to various etiologies. Clinical and occult heart involvement is frequently observed in patients with rheumatic diseases and is associated with increased morbidity and mortality. Cardiac disease in autoimmune disorders encompasses different pathophysiological mechanisms including inflammation and involving either the myocardium or the coronary/pulmonary vessels. Although the major trigger for the synthesis and release of NP is myocardial strain, there is also some support for the concept that inflammation stimulates the neurohormonal system of the heart leading to increased production of NP. Recent studies have focused on the association of NP and inflammation in the context of rheumatic diseases, suggesting that up-regulation of neurohormonal axis in these conditions is linked with inflammation. Additionally the NP have a well-documented role in the diagnostic work-up of patients with connective tissue disease who are at increased risk of developing pulmonary hypertension, as the right ventricular overload results in increased NP synthesis and release. However the precise role of NP in the assessment and the management of cardiovascular risk in patients with rheumatic diseases is yet to be established. In the current article we discuss the pathophysiologic mechanisms involved in enhanced NP expression in patients with rheumatic disorders and their potential clinical implication in daily practice.