Abnormal microvascular perfusion, including decreased functional capillary density and increased blood flow heterogeneity, is observed in early stages of the systemic inflammatory response to infection and appears to have prognostic significance in human sepsis. It is known that improvements in systemic hemodynamics are weakly correlated with the correction of microcirculatory parameters, despite an appropriate treatment of macrohemodynamic abnormalities. Furthermore, conventional hemodynamic monitoring systems available in clinical practice fail to detect microcirculatory parameter changes and responses to treatments, as they do not evaluate intrinsic events that occur in the microcirculation. Fortunately, some bedside diagnostic methods and therapeutic options are specifically directed to the assessment and treatment of microcirculatory changes. In the present review we discuss fundamental aspects of septic microcirculatory abnormalities, including pathophysiology, clinical monitoring, and potential therapies.