Ischemia, being defined as blood supply deficiency is involved in the pathogenesis of a number of life-threatening conditions such as myocardial infarction and cerebral stroke. Assessment of the molecular pathology of these conditions has led to identification of the role of reperfusion in induction and aggravation of tissue injury and necrosis. Thus, the term "ischemia/ reperfusion (I/R) injury" has been introduced. This process involves aberrant regulation of the mitochondrial function, apoptotic and autophagic pathways and signal transducers. More recently, non-coding RNAs including long non-coding RNAs (lncRNAs) ad microRNAs (miRNAs) have been shown to influence I/R injury. Animal studies and clinical investigations have shown up-/down-regulation of tens of lncRNAs and miRNAs in this process. In the current study, we summarize the role of these transcripts in the pathophysiology of I/R injury and their potential as biomarkers for detection of extent of tissue injury.