Myocardial edema is a hallmark of ischemia-reperfusion-related cardiac injury. Ischemia-reperfusion has been shown to result in degradation of the endothelial glycocalyx. The glycocalyx is the gel-like mesh of polysaccharide structures and absorped plasma proteins on the luminal side of the vasculature, and in the past decade has been shown to play an important role in protection of the vessel wall, including its barrier properties. Prevention of glycocalyx loss or restoration of a damaged glycocalyx may be a promising therapeutic target during clinical procedures involving ischemia-reperfusion.