Atrial natriuretic peptide (ANP) is a cardiac peptide with multiple physiological effects, including natriuresis, blood pressure regulation, and renin-angiotensin-aldosterone system (RAAS) antagonism. Pre-proANP is synthesized in the atria and must be extensively cleaved by the protease corin to produce the mature 28 amino acid ANP. The downstream signaling pathway of ANP acts through the guanylyl cyclase receptor and the second messenger cGMP. Studies on ANP’s physiological effects have demonstrated its activity on channels present in the apical membrane in the renal nephron, potentially inhibiting or decreasing sodium reabsorption. Recent research has also identified several clinical conditions, such as dilated cardiomyopathy, renal failure, and aging, associated with increased and decreased ANP levels. ANP levels could serve as a potential biomarker for diagnosis of acute stages of heart failure, and ANP infusion could have a role in the management of acute or chronic heart failure.