Correlation between blood pressure (BP) target organ damage, cardiovascular risk, and long-term prognosis is greater for ambulatory monitored (ABPM) than daytime in-clinic measurements. Additionally, consistent evidence of numerous studies substantiates the ABPM-determined asleep BP mean is an independent and stronger predictor of risk and incidence of end-organ injury and cardiovascular events than the awake or 24-h means. Hence, cost-effective control of sleep-time BP is of great clinical relevance. Ingestion time, according to circadian rhythms, of hypertension medications of six different classes and their combinations significantly impacts beneficial and/or adverse effects. For example, because the high-amplitude circadian rhythm of the renin-angiotensin-aldosterone system activates during nighttime sleep, bedtime versus morning ingestion of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers better controls the asleep than awake BP means, with additional benefit independent of terminal half-life of converting the 24-h BP profile into more normal dipper patterning. Recent findings authenticate therapeutic reduction of sleep-time BP, best achieved when the full daily dose of ≥1 hypertension medications is routinely ingested at bedtime, is the most significant independent predictor of lowered cardiovascular and cerebrovascular risk.