Abstract Primary aldosteronism (PA) is a condition that is still largely overlooked, resulting in a considerable burden of mortality and morbidity. This is despite decades of clinical and translational research on the deleterious effects of aldosterone on the cardiovascular system and the publication of several guidelines and consensuses on its diagnosis and treatment. One of the main reasons for the low rate of testing is the difficulty of screening patients on antihypertensive therapy that potentially interferes with aldosterone and renin levels and thus confound the interpretation of the aldosterone to renin ratio, the accepted and conventionally used screening test. To avoid interference, usually the therapies that affect the renin-angiotensin aldosterone system are withdrawn and substituted with noninterfering medications. However, in many cases the screening test can be confidently interpreted even when such therapies are not discontinued. In this review, we will evaluate the effects of antihypertensive therapies on the screening test for PA and suggest a practical approach for its interpretation.