The　acute　phase　C-reactive　protein　(CRP)　is　mainly　synthesized　and　secreted　by　the　liver　in　a　cytokine-mediated　response　to　infection　or　inflammation　and　circulates　as　a　pentamer　(pCRP)　in　plasma.　Recent　studies　indicate　that　CRP　is　not　only　a　marker　but　is　directly　involved　in　inflammation.　CRP　has　a　vital　role　in　host　defense　and　inflammation,　metabolic　function　and　scavenging　through　its　ability　for　calcium　depended　binding　to　exogenous　and　endogenous　molecules　having　phosphocholine　followed　by　activation　of　the　classical　complement　pathway.　Accumulating　evidence　indicates　that　pCRP　dissociates　into　monomeric　CRP　(mCRP)　and　most　proinflammatory　actions　of　CRP　are　only　expressed　following　dissociation　of　its　native　pentameric　assembly　into　mCRP.　The　dissociation　of　CRP　into　mCRP　altogether　promotes　the　ligand-binding　capability.　mCRP　emerges　to　be　the　main　conformation　of　CRP　that　participates　in　the　regulation　of　local　inflammation,　however,　little　is　identified　concerning　what　triggers　the　significantly　enhanced　actions　of　mCRP　and　their　binding　to　diverse　ligands.　The　separation　of　mCRP　from　pCRP　may　be　a　direct　relationship　between　CRP　and　inflammation.　Here　we　review　the　current　literature　on　CRP　dissociation　and　its　interaction　with　different　ligands.　The　possibility　to　avoid　the　generation　of　the　proinflammatory　potential　of　mCRP　has　driven　therapeutic　approaches　by　targeting　the　dissociation　mechanism　of　pCRP　or　inhibition　of　mCRP　itself　during　inflammation.