The natriuretic peptide system includes three known peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). They contribute to the regulation of cardiovascular homeostasis through diuretic, natriuretic, and vasodilatory properties. Among them, ANP has received particular attention because of its effects on blood pressure regulation and cardiac function. Although the potential for its therapeutic application in the treatment of hypertension and heart failure has been evaluated in several experimental and clinical investigations, no pharmacological approach directly targeted at modulation of ANP levels has ever reached the stage of being incorporated into clinical practice. Recently, ANP has also received attention as being a possible cardiovascular risk factor, particularly in the context of hypertension, stroke, obesity, and metabolic syndrome. Abnormalities in either peptide levels or peptide structure are thought to underlie its implied role in mediating cardiovascular diseases. Meanwhile, BNP has emerged as a relevant marker of left ventricular (LV) dysfunction and as a useful predictor of future outcome in patients with heart failure. This review deals with the major relevant findings related to the cardiovascular and metabolic effects of natriuretic peptides, to their potential therapeutic use, and to their role in mediating cardiovascular diseases.