Reduced microvascular perfusion has been implicated in organ dysfunction and multiple organ failure associated with severe sepsis. The precise mechanisms underlying microvascular dysfunction remain unclear, but there are considerable experimental data showing reduced microcirculatory flow, particularly of small vessels, and increased heterogeneity. With the development of newer imaging techniques, human studies have also been conducted and have given rise to similar findings. Importantly, the degree of microvascular disturbance and its persistence is associated with poorer outcomes. The ability to influence these changes may result in better outcomes and bedside systems, enabling direct visualization of the microcirculation, which will help in the assessment of ongoing microcirculatory dysfunction and its response to established and new therapeutic interventions.