The microcirculation plays a crucial role in the interaction between blood and tissues in physiological pathophysiological pharmacological and clinical states. Despite its significant role in numerous diseases including, hypertension diabetes, sepsis or multiple organ failure, visible and near-infrared light, offer a window into human and animal tissues due to reduced scattering and absorption. We review orthogonal polarization spectral (OPS) imaging method for direct visualization and quantitative assessment of human microcirculation at the bedside are limited. OPS imaging is a relatively new noninvasive method for assessment of human microcirculation without using fluorescent dyes. Recent clinical studies using OPS imaging in various pathological states have shown a wide spectrum of different clinical applications with evident impact on the diagnosis, treatment or prognosis assessment. Thus, there is a great effort to validate OPS imaging for various clinical purposes. The principles of OPS imaging, validation studies, its advantages, limitations, methods of quantitative assessment and current experience in clinical practice are also discussed.