A better understanding of the viability and virulence of putative endodontic pathogens may help explain the mechanism, different clinical presentations of endodontic infections and inturn contribute to identification of therapeutic targets. This study attempts to provide an insight into the diverse range of microflora that infect the root canal system. Their virulence factors and host response are discussed along with the mechanism of establishment of pulp and periradicular lesions. The current advancements in molecular methods of isolation and detection of previously unidentified micro organisms have been discussed elaborately along with the role of biofilms in intra radicular and extraradicular infections.