The irisin, recently identified novel molecule, has been shown to be secreted from fibronectin type III domain containing 5 (FNDC5) of skeletal muscle by an unknown protease. It has been proposed that this molecule plays an important role in converting the white adipose tissue to brown adipose tissue and regulating the energy expenditure. Apart from this, its expression and role in various other conditions such as inflammation, hippocampal neurogenesis, aging and other metabolic conditions have been reported. However, due to conflicting results, several issues have been raised regarding its expression, cleavage, circulating levels, detection, excretion, designation, etc.Complete literature survey was performed using PubMed database search to gather available information regarding FNDC5/irisin.The present review discussed on the discovery of irisin, its possible role in physiological and pathological conditions and controversies. It also discussed the current challenges and future perspectives.