Microvascular dysfunction is a frequent complication of many chronic and acute conditions, especially in the critically ill. Moreover, the severity of microvascular alterations is associated with development of organ dysfunction and poor outcome. The complexities and heterogeneity of critical illness, especially in the elderly patient, requires more mechanistically oriented clinical trials that monitor the effectiveness of existing therapies and of those to come. Recent advances in the ability to obtain physiologically based assessments of microcirculatory function at the bedside will make microcirculatory-guided resuscitation a point of care reality.