Diagnosis of resistant hypertension (RH) is currently based upon awake-time office blood pressure (BP). An increasing number of studies have documented abnormally elevated sleep-time BP in most RH patients, indicating that diagnosis of true RH cannot be determined solely by comparison of office BP with either patient awake-time BP self-measurements or awake-BP mean from ambulatory monitoring (ABPM), as is customary in the published literature. Moreover, the ABPM-determined sleep-time BP mean is an independent and stronger predictor of cardiovascular and cerebrovascular disease (CVD) risk than either daytime office/ABPM-derived awake or 24-hour means. Results of the recently completed MAPEC (Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares) prospective outcomes study, which included a large cohort of RH patients, established that time of treatment relative to circadian rhythms constituted a critically important yet often neglected variable with respect to BP control. The study found that bedtime versus morning ingestion of the full dose of ≥1 BP-lowering medications resulted in both better therapeutic normalization of sleep-time BP and reduced CVD morbidity and mortality, including in RH patients. Accordingly, ABPM is highly recommended to properly diagnose and manage true RH, with a bedtime hypertension medication regimen as the therapeutic scheme of choice.