Infections caused by extracellular Gram positive bacteria are still a major health problems. Better understanding of the mechanisms underlying immune responses to these organisms is key to develop pharmacological agents, including vaccines, to control these infections. The objective of this review is to highlight the importance of nucleic acid-sensing, intracellular Toll-like receptors in innate immune recognition and in host defenses against extracellular bacteria. Toll-like receptors 7 and 9 have a major role in inducing host-protective type I interferon responses in conventional dendritic cells in response to streptococci and other extracellular gram positive bacteria. Moreover an as yet unidentified MyD88-dependent receptor is likely responsible for proinflammatory cytokine induction in response to these pathogens.