Primary aldosteronism (PA) is common and associated with morbidity excessive for degree of hypertension, and reduced quality of life, all reversible with specific surgical or medical treatment. Optimal detection requires accurate laboratory approaches and awareness of potential confounders. In addition to factors previously recognized to affect the plasma aldosterone/renin ratio (ARR; antihypertensives, posture, time of day, dietary salt and plasma potassium), recent studies have drawn attention to effects of gender, and the potential for false positives during the luteal phase of the menstrual cycle and in women receiving estrogen-containing contraceptive agents when direct renin concentration (but not plasma renin activity) is used. Selective serotonin reuptake inhibitors lower the ARR (potential for false negatives). Fludrocortisone suppression testing is probably the most reliable means of definitively confirming or excluding PA, but requires a five day inpatient stay. A new approach, upright (seated) saline infusion suppression testing (SST), has shown excellent reliability in a recent pilot study, with much greater sensitivity than conventional recumbent SST, and requiring only a morning outpatient visit. Differentiation of unilateral (surgically correctable) from bilateral (usually treated medically) PA is essential for optimal management selection. The most reliable approach, adrenal venous sampling (AVS) requires considerable expertise. Optimization of AVS cannulation success rates requires experience and high throughput and can be enhanced by using computed tomography to localize the adrenal veins and point-of-care cortisol testing. Assay reliability is essential for accurate PA workup. The introduction into clinical practice of highly reliable, high-throughput mass spectrometric (MS) methods of measuring aldosterone has represented a major advance. MS approaches to assessing renin/angiotensin activity are in development. Finally, recent years have seen an explosion in knowledge concerning genetic bases of PA, with somatic mutations in genes encoding ion channels or pumps detected in aldosterone-producing adenomas and ion channel germline mutations causing rare familial forms.