Pulsatility seems to have a teleological role because evolutionary hierarchy favors higher ordered animals with more complex, multichamber circulatory systems that generate higher pulse pressure compared with lower ordered animals. Yet despite years of such natural selection, the modern generation of continuous-flow left ventricular assist devices (CF-LVADs) that have been increasingly used for the last decade have created a unique physiology characterized by a nonpulsatile, nonlaminar blood flow profile with the absence of the usual large elastic artery Windkessel effect during diastole. Although outcomes and durability have improved with CF-LVADs, patients supported with CF-LVADs have a high rate of complications that were not as frequently observed with older pulsatile devices, including gastrointestinal bleeding from arteriovenous malformations, pump thrombosis, and stroke. Given the apparent fundamental biological role of the pulse, the purpose of this review is to describe the normal physiology of ventricular-arterial coupling from pulsatile flow, the effects of heart failure on this physiology and the vasculature, and to examine the effects of nonpulsatile blood flow on the vascular system and potential role in complications seen with CF-LVAD therapy. Understanding these concomitant vascular changes with CF-LVADs may be a key step in improving patient outcomes as modulation of pulsatility and flow characteristics may serve as a novel, yet simple, therapy for reducing complications.