Etiopathogenesis of oral submucous fibrosis (OSF) is been studied for long time and still a fully satisfactory explanation is not obtained. Areca nut is the main etiological factor which is consumed as pan masala, gutka, mawa, and betel quid. It will interfere with the collegen synthesis and degradation causing the fibrosis. Several other etiological agents such as chilli and nutritional deficiency have been studied. Furthermore, the genetic susceptibility and autoimmune nature of disease have been postulated by some others. Current evidence also implicates collagen-related genes in the susceptibility and pathogenesis of OSF.