Sepsis is an often-fatal response of the immune system against microbial pathogens. The molecular mechanisms that have been designed to protect the host from invading pathogens are responsible for the damage and injury. It is now widely known that this crucial response of the immune system is mediated by innate immunity, which employs a plethora of pattern recognition receptors that recognise motifs expressed by pathogens. A lack of knowledge of the mediators involved in innate recognition has led to unsuccessful attempts at designing effective therapeutic interventions for sepsis. However, in recent years, great leaps forward have been achieved in our knowledge of these mediators. In this review we attempt to unravel the molecular mechanisms underlying bacterial recognition, particularly recognition of bacterial lipopolysaccharide, and we propose future potential therapeutic targets for septic shock.