The importance of the role played by bacteria in the pathogenesis of pulpal and apical disease has been established. One of the characteristics of apical periodontitis is apical bone resorption, which is due to apical immune response to bacterial infection. Recently, novel bacterial complex lipid called phosphorylated dihydroceramides has been discovered to be of inflammatory activators. The bacterial lipids stimulate prostaglandin E2, IL-6, and TNF-a secretion, inhibit osteoblast differentiation and function, and induce osteoclast formation. The biological activities are in Toll-like receptor 2 (TLR2)-dependent manner. These new findings imply that bacterial lipids could be important virulent factors that cause apical bone resorption. Future investigations may determine the significance of the bacterial lipids in the pathogenesis and treatment of endodontic diseases.