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Although mechanical circulatory support devices should theoretically work in concert with guideline-directed medical therapy, cardiac resynchronization and inotropic and vasopressor agents designed to support myocardial performance and enhance left ventricle recovery, this does not always occur. Each therapy and intervention may result in vastly different and sometimes deleterious effects on vascular afterload. Although best described by a combination of both steady-state and pulsatile components, the latter is frequently overlooked when mean arterial pressure or systemic vascular resistance alone is used to quantify vascular afterload in advanced heart failure and cardiogenic shock. In this state-of-the-art review, we examine what is known about vascular afterload in advanced heart failure and cardiogenic shock, including the use of temporary and permanent mechanical circulatory support systems. Importantly, we outline 4 key components for a more complete assessment of vascular afterload. 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