Circulating cardiac natriuretic peptide levels are being used increasingly in a range of clinical circumstances. Since it is evident that drugs used in the treatment of cardiovascular disorders can modulate natriuretic peptide levels, we here review the literature documenting these effects. Diuretics, blockers of the renin-angiotensin system, vasodilator agents, dopamine-like agonists, amiodarone, and perhaps allopurinol and statins suppress natriuretic peptide levels, most obviously in heart failure. Beta-blockers stimulate natriuretic peptide concentrations in hypertensive subjects, whereas in heart failure they have little effect or are stimulatory in the short term and inhibitory with sustained therapy. Digitalis compounds and aspirin tend to increase natriuretic peptide levels, and calcium channel blocking agents have varying effects depending on the individual drug and duration of administration. The effects of other drugs are less clear. Additional information is needed regarding the effects of medications along with dissection of the role of altered cardiac secretion versus changes in plasma clearance as explanation for drug-induced perturbations in natriuretic peptide concentrations. In the meantime, clinicians need to consider the known effects of medications when interpreting plasma levels of the cardiac natriuretic peptides.