C-reactive　protein　(CRP)　is　a　non-specific　diagnostic　marker　of　inflammation　and　an　evolutionarily　conserved　protein　with　roles　in　innate　immune　signaling.　Natural　CRP　is　composed　of　five　identical　globular　subunits　that　form　a　pentamer,　but　the　role　of　pentameric　CRP　(pCRP)　during　inflammatory　pathogenesis　remains　controversial.　Emerging　evidence　suggests　that　pCRP　can　be　dissociated　into　monomeric　CRP　(mCRP)　that　has　major　roles　in　host　defenses　and　inflammation.　Here,　we　discuss　our　current　knowledge　of　the　dissociation　mechanisms　of　pCRP　and　summarize　the　stepwise　conformational　transition　model　to　mCRP　to　elucidate　how　CRP　dissociation　contributes　to　proinflammatory　activity.　These　discussions　will　evoke　new　understanding　of　this　ancient　protein.