As with all angiotensin II type 1 receptor (AT₁) antagonists, losartan is indicated for the treatment of hypertension. It may also delay progression of diabetic nephropathy, and is also indicated for the reduction of renal disease progression in patients with type 2 diabetes, hypertension and microalbuminuria (>30 mg/24 hours) or proteinuria (>900 mg/24 hours).

Although clinical evidence shows calcium channel blockers and thiazide-type diuretics are preferred first-line treatments for most patients (from both efficacy and cost points of view), an angiotensin II receptor antagonist such as losartan is recommended as first-line treatment in patients under the age of 55 who cannot tolerate an ACE inhibitor. The LIFE study demonstrated losartan was significantly superior to atenolol in the primary prevention of adverse cardiovascular events (myocardial infarction or stroke), with a significant reduction in cardiovascular morbidity and mortality for a comparable reduction in blood pressure. A study hints that losartan has a beneficial effect on mitochondria by reversing age related dysfunction in maintaining normal blood pressure and cellular energy usage.