Hypertension is a major cause and contributor to stroke, heart and kidney disease. Despite the development of an arsenal of medication to treat hypertension over the past half-century, adequate treatment continues to be a major problem in the United States. The Third National Health and Nutrition Examination Survey (NHANES-III) shows that only 29% of hypertensive patients reach a blood pressure less than 140/90 mm Hg. Resistant hypertension is defined as a blood pressure greater than 140/90 mm Hg despite a rational combination of three or more blood pressure medications including a diuretic. The prevalence of true resistant hypertension in hypertension clinics is only about 11-13%. Higher prevalence rates are evident in populations with evidence of end-organ disease such as cardiac or renal disease where lower blood pressure targets have now been established. Ascertaining the possible cause(s) for resistant hypertension is a challenge to all clinicians, but critical in eventual determination of a therapeutic solution. The following review will hopefully help guide clinicians in their discernment of causes and potential treatments for resistant hypertension. The diagnosis and treatment of the more common secondary causes will be described and treatment options for patients with resistant hypertension are discussed. Newer options, some still under clinical investigation, will be described and their future utility will be discussed. (Cardiol J 2007; 14: 329-339)