Microcirculation plays a crucial role in the interaction between blood and tissue both in physiological and pathophysiological states. Orthogonal polarization spectral (OPS) and Side stream dark field (SDF) imaging are relatively new noninvasive methods that allow the investigation of mucosal sites, especially sublingual area, particularly in critically ill patients. OPS imaging has been validated against conventional capillary microscopy, results demonstrated that OPS images provided similar values for RBC-velocity and capillary diameter as those measured by conventional capillary microscopy. Despite some limitations, sublingual microcirculation has been considered as a possible surrogate measure for splanchnic blood flow. There are several areas in human medicine, where observation of sublingual microcirculatory bed has been carried out – different kinds of shock, cardiac arrest, effect of various treatments, drugs and extreme physiological conditions as well. Early detection of microvascular abnormality seems to be a key factor to start early therapeutic intervention in order to reverse microvascular dysfunction, to maintain efficient microvascular flow and to contribute to better clinical outcome. In experimental setting, observing sublingual microcirculation is an important part of any research focused on the role of microcirculation during various diseases models and to assess effect of different treatment modalities on microcirculation.