The introduction of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, i.e., statins, constitutes a milestone in the prevention of cardio- and cerebrovascular disease. The effects of statins extend far beyond their effects on cholesterol levels: pleiotropic effects include vasoprotective mechanisms, comprising improved endothelial function, increased bioavailability of nitric oxide, immunomodulatory and antiinflammatory properties, stabilization of atherosclerotic plaques, as well as antioxidant and stem cell-regulating capacities. Large clinical trials have clearly demonstrated that statins reduce the risk of myocardial infarction and stroke. Recent experimental and clinical data have demonstrated that in addition to risk reduction, statins may also improve outcome after stroke and myocardial infarction, even when statins were administered after the event. Moreover, abrupt discontinuation of statin therapy after acute cardio- or cerebrovascular events may impair vascular function and increase morbidity and mortality. Beyond stroke, statin treatment also has been shown to provide protective effects in critically ill patients, e.g., after major surgery, sepsis, or in patients at high-vascular risk. However, although large randomized controlled trials are missing, ongoing trials will clarify the impact of acute statin treatment in these conditions. Although evidence is presently limited, acute statin therapy is emerging as a new therapeutic avenue for the treatment of the critically ill. Until now, statins were only available as oral drugs. An IV formulation may be warranted for acute treatment of severely ill patients, for example, those who are unable to swallow or scheduled for surgery. Hydrophilic statins would be suitable for an IV formulation and have been safely tested in healthy volunteers.