Mannose binding lectin (MBL) is an important element of the innate immune system. MBL binding leads to activation and cleavage of C3 and C4 suggesting the role of MBL pathway for opsonization and/ phagocytosis. The role of adaptive immune response in development of pathogenic autoantibodies in various autoimmune diseases is well understood. The link between innate and acquired immunity is helpful for understanding the immunopathogenesis of autoimmune diseases. Evidence that innate immune system could lead to autoimmunity is growing with the major recent concept of autoimmune disease pathogenesis is related to impaired apoptotic cell clearance. MBL have been demonstrated to facilitate clearance of apoptotic cells in vivo and in vitro. Low MBL serum levels resulting in impaired apoptotic clearance have shown to enhance the risk for infection and high MBL serum levels and high MBL activity have been associated with inflammatory autoimmune diseases like Systemic Lupus Erythematosus (SLE) that in turn results in to tissue damage and finally leads to organ damage. Serum MBL levels fluctuate during the course of SLE disease activity and MBL genotypes have been found to be useful in assessing the risk of infection during immunosuppressive treatment the majority of the SLE patients receive. This review focuses on the genetic and molecular characteristics of MBL and discusses MBL disease association in autoimmunity with special emphasis on SLE.