PATHWAY-2 used a randomized crossover design to compare commonly used fourth-line options in patients with resistant hypertension already receiving an ACE inhibitor or ARB, calcium-channel blocker and thiazide-type diuretic. Spironolactone produced the largest reduction in home systolic blood pressure compared with bisoprolol or doxazosin and was particularly effective in patients with higher baseline renin suppression. The study strengthened the concept that resistant hypertension often has a substantial mineralocorticoid component and that aldosterone receptor blockade can be highly effective. For internists, the lesson is to confirm true resistance before adding a fourth drug: adherence, measurement technique, excess sodium intake, interacting medicines and secondary causes should all be assessed. Screening for primary aldosteronism, obstructive sleep apnea and renal disease becomes especially relevant when the clinical picture is suggestive. Spironolactone requires monitoring of potassium and kidney function, but its low cost and strong evidence base make it an important practical option. The study also illustrates how home BP measurement can support more reliable therapeutic decisions than office readings alone.