This review is a thoughtful attempt to summarize the current knowledge of irisin and its effective role in mediating vascular tone. Exercise is a mainstay of prevention of chronic, non-communicable diseases, type 2 diabetes and cardiovascular disease in particular. Irisin, a novel myokine produced in response to exercise/physical activity, leads to increased energy expenditure by stimulating the ‘browning’ of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. The action of irisin on different targeted tissues or organs in human being has revealed its physiological functions for promoting health or executing the regulation of variety of metabolic diseases. It is believed that understanding irisin’s function may be the key to comprehend many diseases and their development. It has been demonstrated that irisin plays a key role in metabolic regulation, energy expenditure and glucose homeostasis. New findings from various studies carried out in both animals and humans suggest that irisin might also have other favorable effects, such as modulating vascular activity, thus mediating many exercise-induced health benefits. Experimental findings suggest that irisin might be a useful agent for treating abnormal vasoconstriction-related diseases such as hypertension. However, data on the role and function of irisin have prompted controversy. More detailed mechanism studies and in vivo studies are necessary to establish the efficacy of irisin for treating hypertension. Another strong limitation to the understanding of irisin mechanisms of action is the lack of knowledge about its receptor, which until now remains unidentified in humans and in animals.