The management of the critically ill polytrauma patient is complex due to the multiple complications and biochemical and physiopathological imbalances. This happened due to the direct traumatic injury, or due to the post-traumatic events. One of the most complex physiopathology associated to the multiple traumas is represented by microvascular damage, subsequently responsible for a series of complications induced through the imbalance of the redox status, severe molecular damage, reduction of the oxygen delivery to the cell and tissues, cell and mitochondrial dead, augmentation of the inflammatory response and finally the installation of multiple organ dysfunction syndrome in this type of patients. A gold goal in the intensive care units is represented by the evaluation and intense monitoring of the molecular and physiopathological dysfunctions of the critically ill patients. Recently, it was intensely researched the use of microRNAs as biomarkers for the specific physiopathological dysfunctions. In this paper we wish to present a series of microRNAs that can serve as biomarkers for the evaluation of microvascular damage, as well as for the evaluation of other specific physiopathology for the critically ill polytrauma patient.