Invading pathogens have pathogen-associated molecular patterns (PAMPs) and tissue injury generates damage-associated molecular patterns (DAMPs), which are recognised by pattern recognition receptors (PRRs). Interaction of PRRs with PAMPs/DAMPs initiates the cellular activation that characterises host response in sepsis syndromes. Inflammasomes and signalosomes generated from these initiator pathways provide the feedback amplifier loops perpetuating host response. This unregulated multi-system activation involves inflammatory pathways, cytokines, coagulation, inducible nitric oxide pathways, the autonomic nervous system and the immune system. This is manifested biologically as microvascular failure, mitochondrial dysfunction and apoptotic changes - surrogates of severity of organ dysfunction in sepsis. HMGB, High mobility group box protein; iNO, inducible nitric oxide; MIF, macrophage migration inhibitory factor.