Impaired microcirculation secondary to underlying vascular endothelial dysfunction is increasingly recognized to play a central role in the pathophysiology associated with numerous postoperative complications. Noxious stimuli, including direct injury from surgical trauma and hypoxia (e.g., ischemia-reperfusion injury), trigger adrenergicinflammatory-thrombotic-immune cascades to impair the microcirculation, with consequent perfusion-related postoperative complications. The endothelium, characterized by exquisite sensitivity to inflammation and low proliferative potential, has limited self-repair capacity that is dependent on circulating bone marrow-derived endothelial progenitor cells for regeneration. As such, the extent to which the endothelial physical and functional integrity is preserved mirrors not only underlying cardiovascular health but is also an important factor in susceptibility to postoperative morbidity. This review explores the effect of perioperative inflammation on the microcirculation and some of the current protective strategies available to clinicians. "Prehabilitation," with preoperative exercise to improve the underlying endothelial function and bone marrow responsiveness for endogenous endothelial repair mechanisms, and anti-inflammatory strategies to limit activation of the endothelial-thrombotic-inflammatory cascades may provide clinical strategies to preserve the microcirculation to engender optimal surgical outcomes.