C-reactive　protein　(CRP)　is　well-known　as　a　sensitive　albeit　unspecific　biomarker　of　inflammation.　In　most　rheumatic　conditions,　the　level　of　this　evolutionarily　highly　conserved　pattern　recognition　molecule　conveys　reliable　information　regarding　the　degree　of　ongoing　inflammation,　driven　mainly　by　interleukin-6.　However,　the　underlying　causes　of　increased　CRP　levels　are　numerous,　including　both　infections　and　malignancies.　In　addition,　low　to　moderate　increases　in　CRP　predict　subsequent　cardiovascular　events,　often　occurring　years　later,　in　patients　with　angina　and　in　healthy　individuals.　However,　autoimmune　diseases　characterized　by　the　Type　I　interferon　gene　signature　(e.g.,　systemic　lupus　erythematosus,　primary　Sjogren＇s　syndrome　and　inflammatory　myopathies)　represent　exceptions　to　the　general　rule　that　the　concentrations　of　CRP　correlate　with　the　extent　and　severity　of　inflammation.　In　fact,　adequate　levels　of　CRP　can　be　beneficial　in　autoimmune　conditions,　in　that　they　contribute　to　efficient　clearance　of　cell　remnants　and　immune　complexes　through　complement　activation/modulation,　opsonization　and　phagocytosis.　Furthermore,　emerging　data　indicate　that　CRP　constitutes　an　autoantigen　in　systemic　lupus　erythematosus.　At　the　same　time,　the　increased　risks　of　cardiovascular　and　cerebrovascular　diseases　in　patients　diagnosed　with　systemic　lupus　erythematosus　and　rheumatoid　arthritis　are　well-established,　with　significant　impacts　on　quality　of　life,　accrual　of　organ　damage,　and　premature　mortality.　This　review　describes　CRP-mediated　biological　effects　and　the　regulation　of　CRP　release　in　relation　to　aspects　of　cardiovascular　disease　and　mechanisms　of　autoimmunity,　with　particular　focus　on　systemic　lupus　erythematosus.