Oral submucous fibrosis (OSF) is a scarring pre-malignant condition with the principal causative agent being the chewing of areca and areca-based products and is considered to be a significant, growing public health problem. Not all chewers are afflicted with this condition. Hence, there is a genetic predisposition to this condition. Hence, this review catalogs the genetic polymorphisms that have been specifically reported to be associated with OSF. Also, it underscores the necessity for controlling for ethnicity and chewing history, apart from age and gender, and also reiterates the unmet need for global multi-centric molecular genotyping studies to develop a comprehensive OSF-specific haplotypic signature.