The molecular mechanisms that have been designed to protect the host from invading pathogens are responsible for sepsis, an often fatal response of the immune system against microbial pathogens. In the past few years, intense research in the field of innate immunity has identified a plethora of pattern recognition receptors that are responsible for bacterial-induced activation. Recognition of bacterial lipopolysaccharide seems to involve a complex orchestration of protein-protein interactions that eventually leads to cellular activation. In this review, we attempt to unravel the dynamic interactions that occur among the different receptors involved and dictate the outcome of the innate immune response.