Hypertension and hypotension are strictly related phenomena, that frequently coexist within the spectrum of cardiovascular autonomic dysfunction, especially at advanced age. Indeed, antihypertensive treatment may predispose to orthostatic and postprandial hypotension, while intensive blood pressure lowering may be responsible for systemic hypotension. Over recent years, systemic and orthostatic hypotension have emerged as important although often neglected risk factors for adverse outcomes, paralleling the widely recognized arterial hypertension. Both hypertension and hypotension are associated with detrimental effects on target organs and survival, thus significantly impacting patients' prognosis, functional autonomy, and Quality of Life. Balancing low and high blood pressure requires accurate diagnostic assessment of blood pressure values and patients' hypotensive susceptibility, which allow for the development of customized treatment strategies based on individual hypo/hypertensive risk profile. The present review illustrates the complex interrelationship between hypotension and hypertension and discusses the relevant prognostic role of these conditions. Additionally, it provides an overview on hypotension detection and treatment in patients with hypertension, focusing on customized diagnostic and therapeutic strategies.